TCRB junctional regions from HLA-B27-restricted T cells and HLA-B27 binding peptides display conserved hydropathy profiles in the absence of primary sequence homology.
Analysis of formal amino acid sequence identity between different TCRB chain (TCRB) hypervariable regions (CDR3) is commonly used to localize relevant sites of TCR antigen interaction or to yield indirect information on unknown corresponding antigens. However, this analysis sometimes fails to demonstrate expected concordances, e.g. between CDR3 from T cell clones of identical reactivity. Since this may be due to ignorance of physico-chemical parameters, we have now use hydropathy profile analysis as an additional method to examine TCRB-CDR3 and putative peptide antigens. Superimposed hydropathy plots (SHOP) of 20 TCRB-CDR3 from HLA-B27-restricted autoreactive and Yersinia enterocolitica-specific synovial cytotoxic T lymphocytes (CTL) isolated from patients with reactive arthritis (ReA) revealed restricted distribution of polar amino acids resulting in characteristically different SHOP profiles between the two CTL groups. Similarly, Yersinia-derived and self nonapeptides known to bind HLA-B27 differed in SHOP profiles. To validate the method we have extended SHOP analysis to published TCRB sequence data from additional TCRB-CDR3 from peptide-specific CTL but not in TCRB from HLA-B27-alloreactive CTL or non-HLA-B27-restricted control CTL. We here demonstrate that SHOP may improve TCR-CDR3 sequence analysis by detection of structural constraints which remain cryptic by conventional sequence analysis. Our data suggest that electrostatic properties rather than rigid sequence motifs determine T cell specificities.
May
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E
Department of Medicine, Johannes Gutenberg-Universität Mainz, Germany.
Duchmann
R
R
Ackermann
B
B
Meyer zum Büschenfelde
K H
KH
Märker-Hermann
E
E
D000595:Amino Acid Sequence; D017124:Conserved Sequence / Q000276:immunology*; D019143:Evolution, Molecular; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D010449:Peptide Mapping; D010455:Peptides / Q000378:metabolism*; D000091402:Prohibitins; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015796:HLA-B27 Antigen; C000717331:PHB2 protein, human; D010455:Peptides; D000091402:Prohibitins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta