Antigenic peptide binding to the mouse major histocompatibility complex class II protein I-Ek. Peptide stabilization of the quarternary structure of I-Ek

1992 ◽  
Vol 114 (9) ◽  
pp. 3506-3511 ◽  
Author(s):  
Stephan N. Witt ◽  
Harden M. McConnell
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Peptide Binding ◽  
Class Ii ◽  
Antigenic Peptide ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex

scholarly journals Modulation of the Major Histocompatibility Complex Class II–Associated Peptide Repertoire by Human Histocompatibility Leukocyte Antigen (Hla)-Do

2000 ◽  
Vol 191 (7) ◽  
pp. 1127-1136 ◽  
Author(s):  
Marieke van Ham ◽  
Marcel van Lith ◽  
Björn Lillemeier ◽  
Esther Tjin ◽  
Ulrike Grüneberg ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
B Cells ◽  
Major Histocompatibility Complex Class ◽  
Antigen Presentation ◽  
Cell Activation ◽  
Peptide Binding ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most class II alleles, peptide binding depends on the catalytic action of human histocompatibility leukocyte antigens (HLA)-DM. HLA-DO is selectively expressed in B cells and impedes the activity of DM, yet its physiological role remains unclear. Cell surface iodination assays and mass spectrometry of major histocompatibility complex class II–eluted peptides show that DO affects the antigenic peptide repertoire of class II. DO generates both quantitative and qualitative differences, and inhibits presentation of large-sized peptides. DO function was investigated under various pH conditions in in vitro peptide exchange assays and in antigen presentation assays using DO− and DO+ transfectant cell lines as antigen-presenting cells, in which effective acidification of the endocytic pathway was prevented with bafilomycin A1, an inhibitor of vacuolar ATPases. DO effectively inhibits antigen presentation of peptides that are loaded onto class II in endosomal compartments that are not very acidic. Thus, DO appears to be a unique, cell type–specific modulator mastering the class II–mediated immune response induced by B cells. DO may serve to increase the threshold for nonspecific B cell activation, restricting class II–peptide binding to late endosomal compartments, thereby affecting the peptide repertoire.

scholarly journals An Alternative Promoter in the Mouse Major Histocompatibility Complex Class II I-Aβ Gene: Implications for the Origin of CpG Islands

1998 ◽  
Vol 18 (8) ◽  
pp. 4433-4443 ◽  
Author(s):  
Donald Macleod ◽  
Robin R. Ali ◽  
Adrian Bird
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cpg Island ◽  
Cpg Islands ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Exon 2 ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex

ABSTRACT Nonmethylated CpG islands are generally located at the 5′ ends of genes, but a CpG island in the mouse major histocompatibility complex class II I-Aβ gene is remote from the promoter and covers exon 2. We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells. The resulting transcript potentially encodes a severely truncated protein which would lack the signal peptide and external β1 domains. The functional significance of the internal CpG island may be to facilitate gene conversion, thereby sustaining the high level of polymorphism seen at exon 2. Deletions of the I-Aβ CpG island promoter reduce transcription and frequently lead to methylation of the CpG island in a transgenic mouse assay. These and other results support the idea that all CpG islands arise at promoters that are active in early embryonic cells.

scholarly journals Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

2001 ◽  
Vol 75 (22) ◽  
pp. 10958-10968 ◽  
Author(s):  
John L. Dzuris ◽  
John Sidney ◽  
Helen Horton ◽  
Rose Correa ◽  
Donald Carter ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Rhesus Macaque ◽  
Peptide Binding ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Hla Dr ◽  
Single Substitution

ABSTRACT Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307–319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV.

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