scholarly journals Conformation-dependent recognition of a protein by T cells requires presentation without processing

1989 ◽  
Vol 259 (3) ◽  
pp. 731-735 ◽  
Author(s):  
M Z Atassi ◽  
G S Bixler ◽  
T Yokoi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Protein Antigen ◽  
Mouse Strains ◽  
Immune Recognition ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
T Cell Lines

Presentation of a protein antigen to T cells is believed to follow its intracellular breakdown by the antigen-presenting cell, with the fragments constituting the trigger of immune recognition. It should then be expected that T-cell recognition of protein antigens in vitro will be independent of protein conformation. Three T-cell lines were made by passage in vitro with native lysozyme of T cells from two mouse strains (B10.BR and DBA/1) that had been primed with the same protein. These cell lines responded well to native lysozyme and very poorly to unfolded (S-sulphopropyl) lysozyme. The response of the T-cell lines to the antigen was major histocompatibility complex (MHC)-restricted. A line from B10.BR was selected for further studies. This line responded to the three surface-simulation synthetic sites of lysozyme (representing the discontinuous antigenic, i.e. antibody binding, sites) and analogues that were extended to a uniform size by a nonsense sequence. T-cell clones prepared from this line were specific to native lysozyme and did not respond to the unfolded derivative. Furthermore, several of these clones showed specificity to a given surface-simulation synthetic site. The exquisite dependency of the recognition by the clones on the conformation of the protein antigen and their ability to recognize the surface-simulation synthetic sites indicate that the native (unprocessed) protein was the trigger of MHC-restricted T-cell recognition.

Naturally Processed Peptides Eluted from Acute Myeloid Leukemia Cells : A Potent Antigen Source for Immunotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1801-1801
Author(s):  
Stephanie Delluc ◽  
Lea Tourneur ◽  
Charlotte Boix ◽  
Anne-Sophie Michallet ◽  
Bruno Varet ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Myeloid Leukemia ◽  
Immune Recognition ◽  
T Cell Lines ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogenous group of diseases characterized by a clonal proliferation of myeloid progenitors. Its poor prognosis with conventional chemotherapy justifies seeking for adjuvant immunotherapeutic approaches to eliminate minimal residual disease. We evaluated an immunotherapeutic strategy that bypass the need for epitope identification and the limitation due to HLA restriction. Naturally processed peptides were extracted by acid elution from AML cells at diagnosis, and loaded on mature dendritic cells (mDCs) derived from autologous monocytes obtained when the patients were in complete remission (CR). We evaluated i) the feasibility to elute naturally processed peptides from AML cells at diagnosis, ii) the capacity of mDCs loaded with eluted peptides (mDC/EP) to stimulate specific T cell lines in vitro. We showed that stimulation by mDC/EP was able to generate anti-leukemic T cells lines from PBMC of 6 AML patients in CR. CD4+ and CD8+ T cells were isolated from T cell lines of 5 patients and analyzed for their proliferation, INF-γ production and cytotoxicity in response to autologous or allogeneic AML targets, or to normal autologous PBMC. We showed that both CD4+ and CD8+ leukemia-specific T cells were generated in vitro by mDC/EP stimulations since proliferation of CD4+ T cells, IFN-γ secretion by CD4+ and CD8+ T cells and cytotoxicity mediated by CD8+ T cells were induced in response to stimulation with autologous AML cells. Furthermore, we could not detect auto-immune recognition of autologous normal PBMC, consistent with the specificity of the T cell response induced by mDC/EP. These results provide the proof of concept for using mDC/EP to vaccinate patients with poor-risk AML, and will soon be evaluated in a phse I/II clinical trial.

scholarly journals CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.

1996 ◽  
Vol 183 (1) ◽  
pp. 67-76 ◽  
Author(s):  
F S Wong ◽  
I Visintin ◽  
L Wen ◽  
R A Flavell ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Nod Mice ◽  
Cd8 T Cell ◽  
Rapid Onset ◽  
Cytotoxic T Cell ◽  
Nonobese Diabetic ◽  
T Cell Lines

T cells play an important role in the pathogenesis of diabetes in the nonobese diabetic (NOD) mouse. CD8 cytotoxic T cell lines and clones were generated from the lymphocytic infiltrate in the islets of Langerhans of young (7-wk-old). NOD mice by growing them on (NOD x B6-RIP-B7-1)F1 islets. These cells proliferate specifically to NOD islets and kill NOD islets in vitro. The cells are restricted by H-2Kd, and all bear T cell antigen receptor encoded by V beta 6. When these CD8 T cell lines and clones are adoptively transferred to irradiated female NOD, young NOD-SCID, and CB17-SCID mice, diabetes occurs very rapidly, within 10 d of transfer and without CD4 T cells.

scholarly journals T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing

1989 ◽  
Vol 86 (17) ◽  
pp. 6729-6733 ◽  
Author(s):  
M Z Atassi ◽  
M Yoshioka ◽  
G S Bixler
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Lines ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Oligomeric Protein ◽  
T Cell Lines ◽  
Antigen Presenting

Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.

scholarly journals The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones.

1986 ◽  
Vol 164 (3) ◽  
pp. 897-910 ◽  
Author(s):  
A Finnegan ◽  
M A Smith ◽  
J A Smith ◽  
J Berzofsky ◽  
D H Sachs ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Staphylococcal Nuclease ◽  
Protein Antigen ◽  
Cell Recognition ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Clones ◽  
T Cell Recognition ◽  
Cell Clones

Previous studies (1) have indicated that the repertoire of murine T cells specific for a potentially complex protein antigen is in fact specific for a limited number of antigenic epitopes on that antigen in association with a given Ia molecule. Since those studies generally analyzed responses to antigens that differ in only a few amino acids from homologous murine molecules, it was possible that tolerance to self proteins was responsible for the limited T cell repertoire seen in responses to closely related proteins. It was therefore of interest to determine whether T cell recognition of a structurally and phylogenetically more distant protein molecule would also show specificity for a limited number of immunodominant peptides on that molecule. A series of experiments was designed to study the antigen fine specificity and MHC restriction of T cell clones specific for the bacterially derived antigen staphylococcal nuclease (Nase). T cell clones generated in (H-2b X H-2a)F1 (B6AF1) T cells were shown to be specific for Nase and to be restricted by either Ab alpha Ab beta or Ek alpha Ek beta. The fine specificity of these clones was then analyzed using cyanogen bromide and tryptic fragments and a series of overlapping 20-amino-acid synthetic peptides corresponding to and spanning the entire sequence of the Nase molecule. Two Ab alpha Ab beta-restricted clones were highly responsive to peptide 91-110, and not to other synthetic Nase peptides. In contrast, seven Ek alpha Ek beta-restricted clones were consistently responsive to peptide 81-100 and not to 91-110 or to other Nase peptides. Certain of these Ek alpha Ek beta-restricted T cells expressed an interesting crossreactivity, in that they responded to peptide 51-70 as well as to 81-100, although the response to 51-70 was characterized by a markedly shifted dose-response curve, indicating a reduced efficiency of activation by this peptide. Analysis of the amino acid sequences of these regions indicates that this unexpected crossreaction may have a structural basis. A single Nase-specific T cell line generated from BALB/c T cells was, in contrast to any of the B6AF1 clones studied, responsive only to peptide 61-80 and not to other peptides, including 81-100 or 91-110. Collectively, these findings show that Nase-specific T cells are responsive to discrete Nase peptides. Moreover, the present findings suggest that in T cell recognition of a complex and highly foreign protein antigen, a limited number of peptide epitopes are preferentially recognized by T cells in association with a given Ia molecule.

Development of Chronic Lymphocytic Leukemia (CLL) Reactive Cytotoxic T Lymphocytes after Non-Myeloablative Hematopoietic Stem Cell Transplant Correlates with Anti-Leukemia Response.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 413-413
Author(s):  
Tetsuya Nishida ◽  
Ana Kostic ◽  
David G. Maloney ◽  
Rainer F. Storb ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Histocompatibility Antigens ◽  
Antitumor Response ◽  
Hematopoietic Stem ◽  
Minor Histocompatibility Antigens ◽  
Cell Responses ◽  
T Cell Lines

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) following non-myeloablative (NM) conditioning is a promising approach for treating patients with advanced fludarabine refractory CLL. In this setting, a graft versus leukemia (GVL) effect mediated by donor T cells is critical for tumor eradication. We have evaluated the development of alloreactive and CLL-reactive cytotoxic T lymphocyte (CTL) responses in patients after NM-HSCT to determine if the generation of detectable T cell responses was associated with an antitumor response. Seven patients with fludarabine refractory CLL were conditioned with fludarabine (30mg/m2 x 3 doses) and total body irradiation (2 Gy) prior to receiving G-CSF mobilized peripheral blood stem cells from an HLA matched donor. Peripheral blood mononuclear cells (PBMC) were obtained from the recipient pretransplant and at intervals after NM-HSCT. When chimerism showed a major proportion of donor CD3+ T cells, the postransplant PBMC were stimulated in vitro with recipient CLL cells from the pretransplant collections. CLL cells lack or express low levels of co-stimulatory and adhesion molecules, and are poor stimulators of T cells in vitro. Thus, prior to their use as stimulators and targets, the CLL cells were activated with CD40 ligand (CD40L), which upregulates costimulatory, adhesion, and MHC molecule expression, and turns CLL cells into effective antigen presenting cells. The cultures were stimulated weekly and supplemented with IL2 and IL7. After two stimulations, the T cell lines were tested for cytotoxicity against donor and recipient target cells including recipient CLL. T cell lines generated from four patients with a good antitumor response after NM-HSCT exhibited cytotoxicity against recipient CLL and EBV transformed B cells (B-LCL), but not against donor B-LCL. By contrast, T cell lines generated from three patients with persistent or progressive disease after NM-HSCT did not have cytotoxicity against recipient CLL, despite the development of GVHD in all patients. Multiparameter flow cytometry and IFN-g secretion assay of T cell lines from patients with an antitumor response showed that both CD8+ and CD4+ T cells produced INF-g in response to recipient CLL. We sorted and expanded CD8+ INF-g+ and CD4+ IFN-g+ T cells and both subsets were able to lyse CLL cells. The cytotoxicity of CD4+ and CD8+ T cells was inhibited completely by concanamycin A, suggesting perforin is the major mechanism for leukemia cell lysis. Twenty-one CD8+ T cell clones specific for distinct minor histocompatibility antigens expressed on CLL were isolated from T cell lines of the four responding patients. Multiple specificities were recognized in three of the four patients. Screening a cDNA expression library has identified the genes encoding two minor histocompatibility antigens recognized by CD8+ T cells, and their characterization is in progress. These findings suggest that the development after NM-HSCT of early, diverse, alloreactive T cell responses specific for antigens expressed by CLL may be an important predictor of outcome. The identification of the antigens recognized may facilitate the development of strategies to evoke an effective antitumor response in a larger fraction of patients.

Adenovirus Specific T-Cell Lines Devoid of Alloreactivity Against Haploidentical Recipients Can Be Obtained Using a Set of Adenovirus Hexon Peptides.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3273-3273
Author(s):  
Patrizia Comoli ◽  
Marco W. Schilham ◽  
Sabrina Basso ◽  
Tamara van Vreeswijk ◽  
Rita Maccario ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Peptide Pool ◽  
Specific Lysis ◽  
Hematopoietic Stem ◽  
Hexon Protein ◽  
T Cell Lines

Abstract Human Adenovirus (HAdV) infection/reactivation may cause life-threatening complications in recipients of hematopoietic stem cell transplantation (HSCT), the highest risk being observed in pediatric recipients of a T-cell depleted allograft from haploidentical family donor. The effectiveness of pharmacological therapy for HAdV infection is still suboptimal. It has been recently demonstrated that cell therapy may offer a unique opportunity to restore antiviral immune surveillance, leading to clearance of infection and prevention/treatment of disease. However, infusion of HAdV-specific T-cells in the haplo-HSCT cohort poses the concern that GVHD may ensue as a consequence of T-cell transfer. We have conducted scale-up experiments to validate a method of in vitro culture to expand T-cells specific for HAdV, based on stimulation of donor peripheral blood mononuclear cells (PBMC) with a pool of 5 30-mer peptides derived from HAdV5 hexon protein, for use in recipients of haplo-HSCT (Veltrop-Duits et al, Eur J Immunol36, p2410; 2006). A total of 20 T-cell lines were generated, starting from a median of 20 × 106 donor PBMC, that yielded a median of 80 × 106 cells. Most of the cell lines obtained included a majority of CD4+ T-lymphocytes, with a lower % CD8+ cells (median and range: 78, 19–94 and 18, 5–58, respectively) but 5/20 lines contained a high number of CD8+ T cells (ranging between 43% and 58%), which were CD56+ and/or TCRγδ+, and in 1 case also 44% NK cells. Eighteen of the 20 T-cell lines were HAdV-specific, since they showed a median proliferation to the HAdV hexon peptide pool and inactivated HAdV of 14615 (95%CI 8924–31532) and 11103 (95%CI 8805–30174) cpm/105 cells after subtraction of background (responders+irradiated autologous PBMC), respectively. HAdV-specific lysis >10% at a 2:1 effector to target (E:T) ratio was observed in 50% of the T-cell lines. The 2 non-specific, as well as the 3 T-cell lines with lower specific activity, included >40% CD8+ T-cells. Production of IFNγ in an ELIspot assay to HAdV hexon peptide pool above 40 SFU/105 cells was observed in 9 out of 13 tested T-cell lines. Evaluation of specific response to hexon peptides in showed a majority of responses to II42 (80%), with 50–60% responses to II50, II57, II61, and II64. Only 2 out of the 20 T-cell lines tested were prevalently alloreactive against the recipient. Of the 18 HAdV-specific lines, 1 showed higher proliferation to patient PBMC than to HAdV (13518 vs 11717 mean cpm), and would have thus been discarded as unsuitable for in vivo use, while the other 17 showed no alloreactivity (14) or alloreactivity between 10 and 23% of specific proliferation (3). None of these 18 T-cell lines showed lysis >5% against recipient PHA blasts in the cytotoxicity assay. Our data show that PBMC stimulation with HAdV hexon protein-derived 30-mer peptides is able to reproducibly induce the generation of HAdV-specific CD4+ T-cell lines with efficient in vitro antiviral response in most HLA-mismatched HSCT donors. The majority of these T-cell lines show low/undetectable alloreactivity against recipient targets, and could therefore be safely employed for adoptive treatment of HAdV complications developing after HSCT from a HLA-haploidentical donor.

scholarly journals T-Cell Growth Transformation by Herpesvirus Saimiri Is Independent of STAT3 Activation

2005 ◽  
Vol 79 (9) ◽  
pp. 5713-5720 ◽  
Author(s):  
Elke Heck ◽  
Doris Lengenfelder ◽  
Monika Schmidt ◽  
Ingrid Müller-Fleckenstein ◽  
Bernhard Fleckenstein ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Herpesvirus Saimiri ◽  
Binding Motif ◽  
New World Primates ◽  
Growth Transformation ◽  
T Cell Lines

ABSTRACT Herpesvirus saimiri (saimirine herpesvirus 2) (HVS), a T-lymphotropic tumor virus, induces lymphoproliferative disease in several species of New World primates. In addition, strains of HVS subgroup C are able to transform T cells of Old World primates, including humans, to permanently growing T-cell lines. In concert with the Stp oncoprotein, the tyrosine kinase-interacting protein (Tip) of HVS C488 is required for T-cell transformation in vitro and lymphoma induction in vivo. Tip was previously shown to interact with the protein tyrosine kinase Lck. Constitutive activation of signal transducers and activators of transcription (STATs) has been associated with oncogenesis and has also been detected in HVS-transformed T-cell lines. Furthermore, Tip contains a putative consensus YXPQ binding motif for the SH2 (src homology 2) domains of STAT1 and STAT3. Tip tyrosine phosphorylation at this site was required for binding of STATs and induction of STAT-dependent transcription. Here we sought to address the relevance of STAT activation for transformation of human T cells by introducing a tyrosine-to-phenylalanine mutation in the YXPQ motif of Tip of HVS C488. Unexpectedly, the recombinant virus was still able to transform human T lymphocytes, but it had lost its capability to activate STAT3 as well as STAT1. This demonstrates that growth transformation by HVS is independent of STAT3 activation.

scholarly journals Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying circumsporozoite protein epitopes.

1994 ◽  
Vol 180 (3) ◽  
pp. 1037-1046 ◽  
Author(s):  
F Schödel ◽  
R Wirtz ◽  
D Peterson ◽  
J Hughes ◽  
R Warren ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Vaccine Development ◽  
High Titer ◽  
Mouse Strains ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
B Virus

The hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for the immunodominant circumsporozoite (CS) protein repeat epitopes of Plasmodium falciparum and the rodent malaria agent P. berghei. For this purpose hybrid genes coding for [NANP]4 (C75CS2) or [DP4NPN]2 (C75CS1) as internal inserts in HBcAg (between amino acids 75 and 81) were constructed and expressed in recombinant Salmonella typhimurium. The resulting hybrid HBcAg-CS polypeptides purified from S. typhimurium were particulate and displayed CS and HBc antigenicity, however, the HBc antigenicity was reduced compared to native recombinant HBcAg. Immunization of several mouse strains with HBcAg-CS1 and HBcAg-CS2 particles resulted in high titer, P.berghei- or P.falciparum-specific anti-CS antibodies representing all murine immunoglobulin G isotypes. The possible influence of carrier-specific immunosuppression was examined, and preexisting immunity to HBcAg did not significantly affect the immunogenicity of the CS epitopes within HBcAg-CS1 particles. Similarly, the choice of adjuvant did not significantly alter the immunogenicity of HBcAg-CS hybrid particles. Immunization in complete or incomplete Freund's adjuvant or alum resulted in equivalent anti-HBc and anti-CS humoral responses. Examination of T cell recognition of HBcAg-CS particles revealed that HBcAg-specific T cells were universally primed and CS-specific T cells were primed if the insert contained a CS-specific T cell recognition site. This indicates that the internal site in HBcAg is permissive for the inclusion of heterologous pathogen-specific T as well as B cell epitopes. Most importantly, 90 and 100% of BALB/c mice immunized with HBcAg-CS1 particles were protected against a P. berghei challenge infection in two independent experiments. Therefore, hybrid HBcAg-CS particles may represent a useful approach for future malaria vaccine development.

scholarly journals T-cell recognition of human haemoglobin. Localization of the full T-cell recognition profile of the β-chain by a comprehensive synthetic strategy

1986 ◽  
Vol 234 (2) ◽  
pp. 449-452 ◽  
Author(s):  
M Yoshioka ◽  
N Yoshioka ◽  
M Z Atassi
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
Mouse Strains ◽  
Cell Recognition ◽  
Beta Chain ◽  
Human Haemoglobin ◽  
T Cell Recognition ◽  
Lymph Node Cells

This paper reports the localization of the regions on the beta-chain that are recognized by T cells from mice immunized with haemoglobin. The 14 overlapping peptides encompassing the entire beta-chain were examined in vitro for their ability to stimulate lymph-node cells from haemoglobin-primed B10.D2 (H-2d) and SJL (H-2s) mice. Several regions of the molecule (T sites) were found to stimulate haemoglobin-primed lymph-node cells. This strategy has enabled the localization of the full profile of T-cell recognition of the beta-chain by these mouse strains. Some of the regions that stimulated T cells appeared to coincide with those recognized by antibodies (i.e. B cells). It is noteworthy that, in addition to sites recognized by both T and B cells, the protein has other sites that are recognized exclusively by T cells and to which no detectable antibody response is directed.

scholarly journals Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells.

1979 ◽  
Vol 149 (5) ◽  
pp. 1208-1226 ◽  
Author(s):  
A Singer ◽  
K S Hathcock ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Helper T Cells ◽  
Cell Recognition ◽  
Helper T Cell ◽  
T Cell Recognition ◽  
Accessory Cells

Requirements for helper T-cell recognition of H-2 determinants expressed on adherent accessory cells and on B cells was individually assessed in the anti-hapten PFC responses to TNP-KLH. Complicating allogeneic effects were minimized or avoided by the use of helper T cells from normal F1 hybrids, parent leads to F1 chimeras, and F1 leads to parent chimeras. The results of both in vitro and in vivo experiments demonstrated that: (a) helper T cells are not required to recognize the identical H-2 determinants on both accessory cells and B cells; (b) helper T cells are required to recognize K or I-A region-encoded determinants expressed on accessory cells; (c) no requirement was observed in vitro or in vivo for helper T-cell recognition of B-cell-expressed H-2 determinants; and (d) no requirement was observed for H-2 homology between accessory cells and B cells. The absence of required helper T-cell recognition of the identical H-2 determinants on both accessory cells and B cells was demonstrated in two ways: (a) naive of KLH-primed (A x B)F1 hybrid helper T cells collaborated equally well with B cells from either parentA or parentB in the presence of accessory cells from either parent; (b) A leads to (A x B)F1 chimeric spleen cells depleted of accessory cells collaborated equally well with accessory cells from either parentA or parentB, even though the B cells only expressed the H-2 determinants of parentA. A requirement for helper T-cell recognition of K or I-A region-encoded H-2 determinants on accessory cells was also demonstrated in two ways: (a) (A x B)F1 leads to parentA chimeric spleen cells depleted of accessory cells collaborated with accessory cells from parentA but not parentB; and (b) (A x B)F1 leads to parentA chimeric helper T cells collaborated with normal F1 B cells only in the presence of parental or recombinant accessory cells that expressed the K or I-A region-encoded determinants of parentA. Although restricted in their ability to recognize H-2 determinants on accessory cells, it was demonstrated both in vitro and in vivo that (A x B)F1 leads to parentA chimeric helper T cells were able to collaborate with B cells from either parentA or parentB. In vitro in the presence of accessory cells from parentA, (A x B)F1 leads to parentA chimeric helper T cells collaborated equally well with B cells from either parent. In addition, the inability of (A x B)F1 leads to parentA chimeric helper T cells to collaborate with (B + accessory) cells from parentB was successfully reversed by the addition of parentA SAC as added accessory cells. In vivo, upon the addition of parentA accessory cells, (A x B)F1 leads to parentA chimeric helper T cells collaborated with parentB B cells in short-term adoptive transfer experiments.

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