Role of Self-Major Histocompatibility Complex/Peptide Ligands in Selection and Maintenance of a Diverse T Cell Repertoire

2000 ◽  
Vol 21 (2-3) ◽  
pp. 331-340 ◽  
Author(s):  
Charles D. Surh ◽  
Bettina Ernst ◽  
Dong-Sup Lee ◽  
Wolfgang Dummer ◽  
Eric LeRoy
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Peptide Ligands ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Histocompatibility Complex

scholarly journals Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex–Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor β Chain

1998 ◽  
Vol 188 (5) ◽  
pp. 897-907 ◽  
Author(s):  
Yoshinori Fukui ◽  
Osamu Hashimoto ◽  
Ayumi Inayoshi ◽  
Takahiro Gyotoku ◽  
Tetsuro Sano ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
Peptide Ligand ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Histocompatibility Complex ◽  
Self Peptides ◽  
Selection Of

The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of α/β-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-β chains with a single rearranged TCR-β irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC–peptide complex express highly restricted TCR-α chains in terms of Vα usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.

The Major Histocompatibility Complex and the T Cell Repertoire

H-2 Antigens ◽  
1987 ◽  
pp. 479-484
Author(s):  
Guy Gammon ◽  
Nilabh Shastri ◽  
Stanley Wilbur ◽  
Shahrzad Sadegh-Nasseri ◽  
John Cogswell ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Histocompatibility Complex

Structural requirements and biological significance of interactions between peptides and the major histocompatibility complex

1989 ◽  
Vol 323 (1217) ◽  
pp. 545-552 ◽  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Complex Formation ◽  
Single Amino Acid ◽  
Relative Role ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Peptide Antigen ◽  
Histocompatibility Complex

Previous studies indicate that T cells recognize a complex between the major histocompatibility complex (MHC) restriction-element and peptide-antigen fragments. Two aspects of this complex formation are considered in this paper: (1) what is the nature of the specificity of the interactions that allows a few MHC molecules to serve as restriction elements for a large universe of antigens; and (2 ) what is the relative contribution of determinant selection (i.e. antigen-MHC complex formation) and T-cell repertoire in determining the capacity of an individual to respond to an antigen ? By analysing single amino acid substitution analogues of a peptide antigen (Ova 325-335) as well as by analysing the structural similarities between unrelated peptides capable of binding to the same MHC molecule, we have been able to document the very permissive nature of the antigen-MHC interaction. Despite this permissiveness of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity. With respect to the question of the relative role of ‘determinant selection' and ‘holes in the T-cell repertoire' in determining immune responsiveness, we present data that suggest both mechanisms operate in concert with one another. Thus only about 30 % of a collection of peptides that in sum represent the sequence of a protein molecule were found to bind to la. Although immunogenicity was restricted to those peptides that were capable of binding to la (i.e. determinant selection was operative), we found that about 40 % of la-binding peptides were not immunogenic (i.e. there were also ‘holes in the T-cell repertoire’).

scholarly journals Michael Bevan: Setting up T cell selection

2007 ◽  
Vol 204 (11) ◽  
pp. 2499-2499
Author(s):  
Hema Bashyam
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Selection ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
T Cell Selection

In the 1970s, Michael Bevan showed that T cells only recognize antigens in cells that have the same type of major histocompatibility complex (MHC) molecule present in the thymus where the T cells mature. His work provided the first clues to how thymic self-MHC molecules select the cells that make up the mature T cell repertoire.

scholarly journals The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product.

1983 ◽  
Vol 158 (4) ◽  
pp. 1077-1091 ◽  
Author(s):  
P Marrack ◽  
R Endres ◽  
R Shimonkevitz ◽  
A Zlotnik ◽  
D Dialynas ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Receptor ◽  
Surface Expression ◽  
High Avidity ◽  
Low Doses ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have examined the role of the murine homologue of Leu-3 T4, L3T4, in recognition of antigen in association with products of the major histocompatibility complex (Ag/MHC) by murine T cell hybridomas. A series of ovalbumin (OVA)/I-Ad-specific T cell hybridomas were ranked in their sensitivity to Ag/I by measuring their ability to respond to low doses of OVA, or their sensitivity to inhibition by anti-I-Ad antibodies. T cell hybridomas with low apparent avidity for OVA/I-Ad, i.e. that did not respond well to low concentrations of OVA and were easily inhibited by anti-I-Ad, were also easily inhibited by anti-L3T4 antibodies. The reverse was true for T cell hybridomas with apparent high avidity for Ag/MHC. We found that the presence of low doses of anti-L3T4 antibodies caused T cell hybridomas to respond less well to low doses of Ag, and to be more easily inhibited by anti-I-Ad antibodies. These results suggested that the role of the L3T4 molecule is to increase the overall avidity of the reaction between T cells and Ag-presenting cells. In support of this idea was the discovery of several L3T4- subclones of one of our L3T4+ T cell hybridomas, D0.11.10. The L3T4- subclones had the same amount of receptor for OVA/I-Ad as their L3T4+ parent, as detected by an anti-receptor monoclonal antibody. The L3T4- subclones, however, responded less well to low doses of OVA, and were more easily inhibited by anti-I-Ad antibodies than their L3T4/ parent. These results showed that the L3T4 molecule was not required for surface expression of, or functional activity of, the T cell receptor for Ag/MHC. The L3T4 molecule did, however, increase the sensitivity with which the T cell reacted with Ag/MHC on Ag-presenting cells.

scholarly journals The Role of Peptides in T Cell Alloreactivity Is Determined by Self–Major Histocompatibility Complex Molecules

2000 ◽  
Vol 191 (5) ◽  
pp. 805-812 ◽  
Author(s):  
Reinhard Obst ◽  
Nikolai Netuschil ◽  
Karsten Klopfer ◽  
Stefan Stevanović ◽  
Hans-Georg Rammensee
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Alloreactive T Cells

By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- and viral peptides, we demonstrate a profound influence of self-MHC molecules on the repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-specific, alloreactive (“allorestricted”) T cells versus T cells recognizing the foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-MHC molecules during positive or negative thymic selection or peripheral survival, much like the repertoire of the self-restricted T cells. In consequence, allorestricted, peptide-specific T cells (that are of interest for clinical applications) are easier to obtain if T cells and target cells express related MHC molecules.

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