title: Cross-reactivity analysis of T cell receptors specific for overlapping HIV-1 Nef epitopes of different lengths.
abstract: Overlapping peptides of different lengths from a certain immunodominant region can be presented by the same HLA class I molecule and elicit different T cell responses. However, how peptide-length specificity of antigen-specific CD8(+) T lymphocytes influence cross-reactivity profiles of these cells remains elusive. This question is particularly important in the face of highly variable pathogens such as HIV-1. Here, we examined this problem by using HLA-B*35:01-restricted CD8(+) T lymphocytes specific for Nef epitopes, i.e., RY11 (RPQVPLRPMTY), VY8 (VPLRPMTY), and RM9 (RPQVPLRPM), in which VY8 and RM9 were contained entirely within RY11, in combination with a T cell receptor (TCR) reconstruction system as well as HLA-B35 tetramers and a set of a single-variant peptide library. The TCR reactivity toward the peptide-length variants was classified into three types: mutually exclusive specificity toward (1) RY11 or (2) VY8 and (3) cross-recognition toward RM9 and RY11. TCR cross-reactivity toward variant peptides was similar within the same peptide-length reactivity type but was markedly different between the types. Thus, TCRs showing similar peptide-length reactivity have shared peptide recognition footprints and thereby similar weakness to antigenic variations, providing us with further insight into the antiviral vaccine design.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Motozono
authors.affiliation: Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan. Electronic address: uenotaka@kumamoto-u.ac.jp.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ueno
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
chemical_list: D000939:Epitopes; D015797:HLA-B35 Antigen; D011948:Receptors, Antigen, T-Cell; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1
keywords: Antigenic peptide; CD8(+) T cell; Cross-reactivity; HIV-1; HLA-B*35:01; TCR