The Journal of Immunology, Vol 153, Issue 10 4458-4467, Copyright © 1994 by American Association of Immunologists

ARTICLES

Diversity and dominance among TCR recognizing HLA-A2.1+ influenza matrix peptide in human MHC class I transgenic mice

S Man, JP Ridge and VH Engelhard
Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville 22908.

The TCR structures of CTL derived from HLA-A2.1 transgenic mice were analyzed to determine features important in the interaction of murine TCR with the HLA-A2.1 + influenza M1(57-68) peptide complex. V beta 8.1 was dominant in 9 of 11 murine CTL lines, although three other V beta segments were also represented. Sequencing of TCR cDNA from a group of six independently derived CTLs that were V beta 8.1-positive demonstrated a restricted set of D-N-J beta sequences and an apparently restricted set of alpha-chains. However, at least five other distinct alpha beta pairs were found among HLA-A2.1 + M1 peptide-specific CTL in the absence of these chains. Consideration of all TCR sequences obtained demonstrated diverse beta-chain CDR3 regions with some restriction in V alpha segment usage and bias in amino acid sequence of alpha-chain CDR3 regions. Nevertheless, the strongest correlation with HLA-A2.1 + M1 specificity was clearly V beta 8.1 usage. Comparison with previously identified human TCR sequences specific for the same Ag-MHC complex revealed that the dominant murine V alpha and V beta segments used were not the homologues of the dominant human V beta and V alpha segments used. These results together with the lack of interspecies conservation in the alpha- and beta-chain CDR3 regions demonstrate that the dominant TCR structures recognizing HLA-A2.1 + M1(57-68) are substantially different between mouse and humans. Different factors may influence Ag-driven selection of the dominant TCRs used in each species.

This article has been cited by other articles:

				E. Cheuk, C. D'Souza, N. Hu, Y. Liu, H. Lang, and J. W. Chamberlain Human MHC Class I Transgenic Mice Deficient for H2 Class I Expression Facilitate Identification and Characterization of New HLA Class I-Restricted Viral T Cell Epitopes J. Immunol., November 15, 2002; 169(10): 5571 - 5580. [Abstract] [Full Text] [PDF]

				A. Ureta-Vidal, H. Firat, B. Perarnau, and F. A. Lemonnier Phenotypical and Functional Characterization of the CD8+ T Cell Repertoire of HLA-A2.1 Transgenic, H-2Kb{degrees}Db{degrees} Double Knockout Mice J. Immunol., September 1, 1999; 163(5): 2555 - 2560. [Abstract] [Full Text] [PDF]

				Y. Men, I. Miconnet, D. Valmori, D. Rimoldi, J.-C. Cerottini, and P. Romero Assessment of Immunogenicity of Human Melan-A Peptide Analogues in HLA-A*0201/Kb Transgenic Mice J. Immunol., March 15, 1999; 162(6): 3566 - 3573. [Abstract] [Full Text] [PDF]

				M. J. Shields, R. Kubota, W. Hodgson, S. Jacobson, W. E. Biddison, and R. K. Ribaudo The Effect of Human beta 2-Microglobulin on Major Histocompatibility Complex I Peptide Loading and the Engineering of a High Affinity Variant. IMPLICATIONS FOR PEPTIDE-BASED VACCINES J. Biol. Chem., October 23, 1998; 273(43): 28010 - 28018. [Abstract] [Full Text] [PDF]

				S. Pascolo, N. Bervas, J. M. Ure, A. G. Smith, F. A. Lemonnier, and B. Perarnau HLA-A2.1-restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from beta 2 Microglobulin (beta 2m) HLA-A2.1 Monochain Transgenic H-2Db beta 2m Double Knockout Mice J. Exp. Med., June 16, 1997; 185(12): 2043 - 2051. [Abstract] [Full Text] [PDF]

				M. Theobald, J. Biggs, J. Hernandez, J. Lustgarten, C. Labadie, and L. A. Sherman Tolerance to p53 by A2.1-restricted Cytotoxic T Lymphocytes J. Exp. Med., March 3, 1997; 185(5): 833 - 842. [Abstract] [Full Text] [PDF]