Analysis of TCRalphabeta combinations used by simian immunodeficiency virus-specific CD8+ T cells in rhesus monkeys: implications for CTL immunodominance.
Immunodominance is a common feature of Ag-specific CTL responses to infection or vaccines. Understanding the basis of immunodominance is crucial to understanding cellular immunity and viral evasion mechanisms and will provide a rational approach for improving HIV vaccine design. This study was performed comparing CTLs specific for the SIV Gag p11C (dominant) and SIV Pol p68A (subdominant) epitopes that are consistently generated in Mamu-A*01(+) rhesus monkeys exposed to SIV proteins. Additionally, vaccinated monkeys were used to prevent any issues of antigenic variation or dynamic changes in CTL responses by continuous Ag exposure. Analysis of the TCR repertoire revealed the usage of higher numbers of TCR clones by the dominant p11C-specific CTL population. Preferential usage of specific TCRs and the in vitro functional TCR-alpha- and -beta-chain-pairing assay suggests that every peptide/MHC complex may only be recognized by a limited number of unique combinations of alpha- and beta-chain pairs. The wider array of TCR clones used by the dominant p11C-specific CTL population might be explained by the higher probability of generating those specific TCR chain pairs. Our data suggest that Ag-specific naive T cell precursor frequency may be predetermined and that this process dictates immunodominance of SIV-specific CD8(+) T cell responses. These findings will aid in understanding immunodominance and designing new approaches to modulate CTL responses.
Hasegawa
Atsuhiko
A
Division of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Moriya
Chikaya
C
Liu
Huining
H
Charini
William A
WA
Vinet
Heather C
HC
Subbramanian
Ramu A
RA
Sen
Pritha
P
Letvin
Norman L
NL
Kuroda
Marcelo J
MJ
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D008253:Macaca mulatta; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
D000956:Antigens, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015684:Gene Products, pol; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; C110764:Mamu-A 01 antigen; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018449:SAIDS Vaccines