Faculty Opinions recommendation of TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection.

ABSTRACT The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

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Effects of HIV-1 Tat on Expression of HLA Class I Molecules

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199603010-00003 ◽

1996 ◽

Vol 11 (3) ◽

pp. 233-240 ◽

Cited By ~ 22

Author(s):

Masanori Matsui ◽

Robert J. Warburton ◽

Patricia C. Cogswell ◽

Albert S. Baldwin ◽

Jeffrey A. Frelinger

Keyword(s):

Hla Class I ◽

Class I ◽

Hla Class I Molecules ◽

Hiv 1

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Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection

Molecular and Cellular Biochemistry ◽

10.1007/s11010-019-03649-x ◽

2019 ◽

Vol 464 (1-2) ◽

pp. 65-71 ◽

Cited By ~ 1

Author(s):

Abaineh Munshea Abitew ◽

Ranbir Chander Sobti ◽

Vijay Lakshmi Sharma ◽

Ajay Wanchu

Keyword(s):

Immune Response ◽

Hla Class I ◽

Class I ◽

Control Analysis ◽

Antigenic Peptides ◽

Human Major Histocompatibility Complex ◽

Hla Class I Molecules ◽

Increased Risk ◽

Exon 11 ◽

Hiv 1

AbstractHuman leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR–RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06–1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56–7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case–control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.

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Adaptive Interactions between HLA and HIV-1: Highly Divergent Selection Imposed by HLA Class I Molecules with Common Supertype Motifs

The Journal of Immunology ◽

10.4049/jimmunol.0903745 ◽

2010 ◽

Vol 184 (8) ◽

pp. 4368-4377 ◽

Cited By ~ 35

Author(s):

Mina John ◽

David Heckerman ◽

Ian James ◽

Lawrence P. Park ◽

Jonathan M. Carlson ◽

...

Keyword(s):

Hla Class I ◽

Divergent Selection ◽

Class I ◽

Hla Class I Molecules ◽

Hiv 1

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Evidence of widespread binding of HLA class I molecules to peptides.

Journal of Experimental Medicine ◽

10.1084/jem.172.3.827 ◽

1990 ◽

Vol 172 (3) ◽

pp. 827-834 ◽

Cited By ~ 40

Author(s):

J A Frelinger ◽

F M Gotch ◽

H Zweerink ◽

E Wain ◽

A J McMichael

Keyword(s):

Monoclonal Antibodies ◽

Binding Assay ◽

Solid Phase ◽

Hla Class I ◽

Class I ◽

T Cell Epitopes ◽

Single Class ◽

Hla Class I Molecules ◽

Solid Phase Binding ◽

Hiv 1

We have tested the binding of HLA class I proteins to peptides using a solid-phase binding assay. We tested 102 peptides, mostly derived from the HIV gag and HIV pol sequences. Most peptides did not bind to any class I protein tested. The pattern of binding among the three class I proteins tested, HLA-A2, -B27, and -B8, was approximately 85% concordant. Further, all five of the known HIV-1 gag T cell epitopes detected by human CTL bound at least one class I protein. Binding of class I to the peptides could be detected either by directly iodinated class I proteins, or indirectly using monoclonal antibodies specific for class I. The binding to the plates could be blocked with MA2.1, which binds in the alpha 1 region of A2, but not by W6/32, which binds elsewhere. The data presented here show that binding of class I to peptides is specific, but that many peptides bind to more than a single class I protein.

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