title: Preferential V beta usage by cytotoxic T cells cross-reactive between two epitopes of HIV-1 gp160 and degenerate in class I MHC restriction.
abstract: The T cell response to HIV-1 gp160 is among the most thoroughly studied immune responses to HIV-1 products. In our previous work, the MHC class I molecule Dd as well as H-2u, p, and q, were found to present P18 and HP53, two determinants of HIV-1 gp160, to CD8+ CTL in mice. We have studied the TCR V beta chain expression in CTL lines, either cross-reactive for these two peptides or specific for P18 alone, in these four different MHC haplotypes. The usage of V beta in T cells showing cross-reaction between these two peptides was remarkably conserved (primarily V beta 8 family, with some use of V beta 14) despite the extensive TCR V beta diversity of the non-cross-reactive CTL, which did not use V beta 8 or 14. This correlation of V beta usage with fine specificity was consistent in H-2d, u, and p (p < 0.01), but not in H-2q. The correlation of V beta use with peptide fine specificity independent of MHC restriction was unexpected. The strong predominance of V beta 8 family TCR was all the more surprising in view of the finding that mice bearing a genomic deletion of V beta 8 can still produce T cells with the cross-reactive phenotype, implying that other V beta chains can produce this specificity. We therefore asked whether the complexes of P18 with H-2d, p, and u are recognized as identical, and observed the surprising result that H-2d, p, and u cells mutually cross-present the peptides P18 and HP53 to allogeneic CTL lines and individual clones of each of the other haplotypes, whereas none of these cross-present to H-2q CTL, nor do H-2q targets present to CTL of the other haplotypes. This degeneracy of MHC restriction is novel for class I molecules. Moreover, the observed restriction in V beta usage occurs only in the unique set of CTL that exhibit both peptide-cross-reactive fine specificity and MHC allogeneic cross-presentation. The observation that a strain of mice in which the V beta 8 family is genomically deleted can still make CTL of this phenotype using another V beta demonstrates the plasticity of the class I MHC-restricted repertoire when the dominating receptor is not available.
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: M
authors.initials: M
authors.lastname: Shirai
authors.forename: M S
authors.initials: MS
authors.lastname: Vacchio
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
authors.forename: J A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes; D017353:Gene Deletion; D015686:Gene Products, env / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000939:Epitopes; D015686:Gene Products, env; D006183:H-2 Antigens; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D016693:Receptors, Antigen, T-Cell, alpha-beta