T cell receptor cross-recognition of an HIV-1 CD8+ T cell epitope presented by closely related alleles from the HLA-A3 superfamily.
HLA-A3 and -A11 share similar peptide-binding motifs, however, it is unclear if promiscuous epitope presentation by HLA-A3 or HLA-A11 is associated with promiscuous TCR recognition. Here, we show that despite widespread cross-presentation of identical HIV-1 peptides in HIV-1-infected individuals expressing HLA-A3 or HLA-A11, peptides presented by HLA-A3 or HLA-A11 commonly exhibited clear immune distinctiveness with exclusive TCR recognition. Yet, using HLA-A3 and HLA-A11 tetramers for testing T cell cross-recognition of the HIV-1 Nef QK10 epitope, we observed in two study persons that specific CD8+ T cell populations were able to cross-recognize this peptide in the context of both HLA-A3 and HLA-A11. This cross-recognition was mediated by single cross-reactive TCRs, as shown by TCR sequencing in conjunction with TCR Vbeta chain immunostaining. In each cross-reactive cell population, multiple TCR beta chain variants were detected in the presence of only one TCR alpha chain variant. Thus, despite distinct TCR recognition of HLA-A3 or HLA-A11 presented HIV-1 peptides in the vast majority of cases, specific TCRs can cross-recognize their antigen in the context of both HLA-A3 and HLA-A11.
Lichterfeld
Mathias
M
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA, USA.
Williams
Katie L
KL
Mui
Stanley K
SK
Shah
Shivani S
SS
Mothe
Bianca R
BR
Sette
Alessandro
A
Kim
Arthur
A
Johnston
Mary N
MN
Burgett
Nicole
N
Frahm
Nicole
N
Cohen
Daniel
D
Brander
Christian
C
Rosenberg
Eric S
ES
Walker
Bruce D
BD
Altfeld
Marcus
M
Yu
Xu G
XG
D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen / Q000276:immunology*; D006801:Humans; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen; D054311:nef Gene Products, Human Immunodeficiency Virus