Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection.
Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8(+) T cell populations in Mamu-A*01(+) rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR beta-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8(+) T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181-189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8(+) T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dprice1@mail.nih.gov
David A
DA
Price
Tedi E
TE
Asher
Nancy A
NA
Wilson
Martha C
MC
Nason
Jason M
JM
Brenchley
Ian S
IS
Metzler
Vanessa
V
Venturi
Emma
E
Gostick
Pratip K
PK
Chattopadhyay
Mario
M
Roederer
Miles P
MP
Davenport
David I
DI
Watkins
Daniel C
DC
Douek
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D007114:Immunization; D008253:Macaca mulatta; D010641:Phenotype; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000662:veterinary; D014765:Viral Vaccines / Q000276:immunology
D015683:Gene Products, gag; D014765:Viral Vaccines