Limited restriction in the TCR-alpha beta V region usage of antigen-specific clones. Recognition of myelin basic protein (amino acids 84-102) and Mycobacterium bovis 65-kDa heat shock protein (amino acids 3-13) by T cell clones established from peripheral blood mononuclear cells of monozygotic twins and HLA-identical individuals.
We have analyzed the TCR-alpha beta repertoire specific for a given peptide/MHC complex by using pairs of HLA-identical individuals ranging from monozygotic twins to unrelated individuals to examine the contribution of genetic background and HLA expression in shaping the potential response to a single antigenic epitope. This panel has been previously defined, demonstrating that the concordance of the peripheral TCR-alpha beta repertoires directly correlates to the level of relation and HLA identity. We have analyzed peptide-specific T cell clones derived from T cell lines from these individuals specific for MHC class II-restricted peptides: Mycobacterium bovis 65-kDa heat shock protein (65-kDa hsp) amino acids (aa) 3-13 (DR3-restricted), and myelin basic protein aa 84-102 (DR2-restricted). DNA sequence analysis was used to determine the composition of the TCR-alpha beta V regions. Although the overall TCR-alpha beta repertoires between individuals were diverse, an intra-individual limited restriction was evident. There was also a limited conservation in the response to the different peptides: high frequencies of V beta 2, 4, 7, 19, V alpha 21, and J alpha 17 responded to the MBP aa84-102, whereas these V/J regions were limited or absent in the 65-kDa hsp aa3-13 repertoire. Similarly, V beta 5.1 and J alpha 9 were increased in the 65-kDa hsp aa3-13 repertoire. Within the CDR3s, motifs could be identified that were similar between twins. Furthermore, one of these motifs resembled CDR3s previously found in corresponding animal models. Similarities could also be seen in the CDR3s of T cell clones sharing V gene usage and peptide specificity. Thus, the in vitro response to antigenic peptides seems to be quite heterogeneous overall and individual specific.
Hawes
G E
GE
Department of Immunohematology, University Hospital Leiden, The Netherlands.
Struyk
L
L
Godthelp
B C
BC
van den Elsen
P J
PJ
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D001483:Base Sequence; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D002999:Clone Cells; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014430:Twins, Monozygotic / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D006680:HLA Antigens; D006360:Heat-Shock Proteins; D004676:Myelin Basic Protein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins