The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized.
Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 Kd. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252-260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170-179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant. H-2 Kd molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/Kd complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.
Maryanski
J L
JL
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Casanova
J L
JL
Falk
K
K
Gournier
H
H
Jaulin
C
C
Kourilsky
P
P
Lemonnier
F A
FA
Lüthy
R
R
Rammensee
H G
HG
Rötzschke
O
O
Servis
C
C
López
J A
JA
D000818:Animals; D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000939:Epitopes; D006183:H-2 Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins