Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.

Abstract

Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.

• Authors: C Brander, K E Hartman, A K Trocha, N G Jones, R P Johnson, B Korber, P Wentworth, S P Buchbinder, S Wolinsky, B D Walker, S A Kalams
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 101 Issue 11 Pg. 2559-66 (Jun 01 1998) ISSN: 0021-9738 [Print] United States
• PMID: 9616227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes
• HLA-A Antigens

Topics

• Acquired Immunodeficiency Syndrome (immunology)
• Chronic Disease
• Epitopes
• HIV-1
• HLA-A Antigens (physiology)
• Hematopoietic Stem Cells (immunology)
• Humans
• T-Lymphocytes, Cytotoxic (immunology)