Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes.
The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR beta-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703(+) individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.
Yu
Xu G
XG
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Room 5212, Charlestown, MA 02129, USA.
Lichterfeld
Mathias
M
Chetty
Senica
S
Williams
Katie L
KL
Mui
Stanley K
SK
Miura
Toshiyuki
T
Frahm
Nicole
N
Feeney
Margaret E
ME
Tang
Yanhua
Y
Pereyra
Florencia
F
Labute
Montiago X
MX
Pfafferott
Katja
K
Leslie
Alisdair
A
Crawford
Hayley
H
Allgaier
Rachel
R
Hildebrand
William
W
Kaslow
Richard
R
Brander
Christian
C
Allen
Todd M
TM
Rosenberg
Eric S
ES
Kiepiela
Photini
P
Vajpayee
Madhu
M
Goepfert
Paul A
PA
Altfeld
Marcus
M
Goulder
Philip J R
PJ
Walker
Bruce D
BD
D000483:Alleles; D019943:Amino Acid Substitution; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013045:Species Specificity
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell