Asymmetric selection of T cell antigen receptor alpha- and beta-chains in HLA-B27 alloreactivity.
Endogenous peptides constitutively bind to class I MHC Ag and are thought to be integral parts of allospecific T cell epitopes. However, allospecific TCR can recognize structural features of the alloantigen as foreign. To define some crucial parameters determining HLA-B27 allorecognition, the structure of TCR alpha- and beta-chains from HLA-B27-specific CTL was analyzed. A strategy, based on V alpha and V beta family-specific oligonucleotides, was used for specific amplification and direct sequencing of TCR-alpha and -beta cDNA. We observed nonrandom usage of V beta segments and recurrent structural motifs within beta-chain junctional regions. In contrast, no structural restrictions were apparent among alpha-chains, even from CTL clones of related fine specificity. These results indicate an asymmetric contribution of TCR alpha- and beta-chains to HLA-B27 allospecificity among the CTL clones analyzed. They suggest recognition of multiple peptides and involvement of beta-chain junctional regions in recognizing shared motifs among some of these peptides.
Lauzurica
P
P
Department of Immunology, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Bragado
R
R
López
D
D
Galocha
B
B
López de Castro
J A
JA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015796:HLA-B27 Antigen; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta