Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents.
BACKGROUND
Differential protein targeting by HIV-specific CD8 T cells is associated with disparate plasma viral loads; however, it is unclear if the quality of these responses differs depending upon the specificity of the targeted epitopes.


METHODS
We examined HIV-specific CD8 T-cell responses in HIV-infected adolescents carrying either an HLA class I allele associated with a favorable prognosis (HLA-B*57) or an allele associated with usual disease progression (HLA-B*35 or HLA-B*53) using interferon-gamma ELISpot and ICS assays.


RESULTS
In an interferon-gamma ELISpot assay, p24 was the dominant protein targeted by B*57 carriers while responses to Nef dominated in B*35 or B*53 positive carriers. This differential protein targeting did not change during 4 years of follow-up. In these chronically infected adolescents, there were no significant differences in the quality of the immunodominant T-cell responses between the B*57 and B*35/B*53 carriers as measured by peptide avidity, degranulation, and immune memory markers. There was a trend towards higher expression of interleukin-2 from B*57-KF11 restricted CD8 T cells although this difference was not significant. Nevertheless both B*57 and B*35/53-restricted responses were relatively potent as reflected by the propensity of CD8 T cells to escape in p24 and Nef, respectively.


CONCLUSIONS
Differential protein targeting rather than the quality of T-cell responses appears to be a major distinguishing feature of HIV-specific CD8 T cells induced in B*57 carriers. These data suggest that viral fitness costs associated with CD8 T-cell pressure is an important factor determining differences in the viral load among HIV-infected patients.
Bansal
Anju
A
Department of Medicine, University of Alabama at Birmingham, Alabama, USA.
Yue
Ling
L
Conway
Joan
J
Yusim
Karina
K
Tang
Jianming
J
Kappes
John
J
Kaslow
Richard A
RA
Wilson
Craig M
CM
Goepfert
Paul A
PA
D000293:Adolescent; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D015797:HLA-B35 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D015683:Gene Products, gag; D016655:HIV Core Protein p24; D006680:HLA Antigens; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; C078438:HLA-B53 antigen; C103707:HLA-B57 antigen; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1