Biased T-cell receptor usage is associated with allelic variation in the MHC class II peptide binding groove

A comprehensive analysis was carried out of the tri-molecular complex of peptide, major histocompatibility class II molecule, and T-cell receptor (TcR) involved in the recognition of the promiscuous HA (306-318) peptide, restricted by one of two closely related HLA-DR alleles, HLA-DRB1*0101 and HLA-...

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Bibliographic Details
Published in:Immunogenetics (New York) 1999-06, Vol.49 (6), p.532-540
Main Authors: Yassine-Diab, B, Carmichael, P, L'Faqihi, F E, Lombardi, G, Deacock, S, de Préval, C, Coppin, H, Lechler, R I
Format: Article
Language:English
Subjects:
Alleles
Genetic Variation
HLA-DR Antigens - immunology
HLA-DRB1 Chains
Humans
Interleukin-2 - biosynthesis
Peptides - immunology
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, alpha-beta - immunology
T-Lymphocytes - immunology
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Summary:A comprehensive analysis was carried out of the tri-molecular complex of peptide, major histocompatibility class II molecule, and T-cell receptor (TcR) involved in the recognition of the promiscuous HA (306-318) peptide, restricted by one of two closely related HLA-DR alleles, HLA-DRB1*0101 and HLA-DRB1*0103. These two DR molecules differ by only three amino acids at positions 67, 70, and 71, in the third variable region of the DRB1 chain. None of the HA (306-318)-specific T-cell clones restricted by these two DR molecules tolerated amino acid substitution at the peptide-binding position 71, despite the fact that the substitution did not interfere with peptide binding. The majority of the DRB1*0103-restricted clones tolerated substitution of the amino acid at the TcR-contacting position 70, while the DRB1*0101-restricted T cells did not. Based usage of TRVA and TRVB segments was observed for the DRB1*0103-restricted clones; in contrast, apparently random usage was seen in the DRB1*0101-restricted T cells. Finally, limiting dilution analysis revealed a lower frequency of T cells reactive with the HA peptide in a DRB1*0103 compared with a DRB1*0101 individual. Taken together these data suggest that biased TcR gene usage may reflect a relatively low precursor frequency of T cells, and the need for clonal expansion of a limited set of high avidity T cells.
ISSN:0093-7711
1432-1211
DOI:10.1007/s002510050531