HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.
BACKGROUND
Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.


RESULTS
In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection.


CONCLUSIONS
These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.
Altfeld
Marcus
M
Kalife
Elizabeth T
ET
Qi
Ying
Y
Streeck
Hendrik
H
Lichterfeld
Mathias
M
Johnston
Mary N
MN
Burgett
Nicole
N
Swartz
Martha E
ME
Yang
Amy
A
Alter
Galit
G
Yu
Xu G
XG
Meier
Angela
A
Rockstroh
Juergen K
JK
Allen
Todd M
TM
Jessen
Heiko
H
Rosenberg
Eric S
ES
Carrington
Mary
M
Walker
Bruce D
BD
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D000483:Alleles; D000940:Antigenic Variation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D016016:Proportional Hazards Models
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D016056:Immunodominant Epitopes