Common Sequence in HIV-1 GP41 and HLA Class II Beta Chains can Generate Crossreactive Autoantibodies with Immunosuppressive Potential Early in the Course of HIV-1 Infection

ABSTRACT Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Batswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Batswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.

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HIV-1 Variation Diminishes CD4 T Lymphocyte Recognition

Journal of Experimental Medicine ◽

10.1084/jem.188.10.1785 ◽

1998 ◽

Vol 188 (10) ◽

pp. 1785-1793 ◽

Cited By ~ 51

Author(s):

Gillian C. Harcourt ◽

Sarah Garrard ◽

Miles P. Davenport ◽

Anne Edwards ◽

Rodney E. Phillips

Keyword(s):

T Lymphocyte ◽

Mononuclear Cells ◽

Antigenic Variation ◽

Class Ii ◽

Hla Class Ii ◽

Peripheral Blood Mononuclear ◽

Altered Peptide Ligands ◽

Peptide Epitopes ◽

Naturally Occurring ◽

Hiv 1

Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4+ T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4+ T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood mononuclear cells from 43 asymptomatic HIV-1+ patients for proliferative responses to HIV-1 antigens. 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c. Nine naturally occurring variants of the p24 Gag epitope were found in the proviral DNA of the individual in whom this response was detected. All variants bound to HLA-DR1, but three of these peptides failed to stimulate a CD4+ T lymphocyte line which recognized the index sequence. Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4+ T lymphocyte line, whereas several natural mutants were not. Importantly, variants detected at both epitopes also failed to stimulate fresh uncultured cells while index peptide stimulated successfully. These results demonstrate that variant antigens arise in HIV-1+ patients which fail to stimulate the T cell antigen receptor of HLA class II–restricted lymphocytes, although the peptide epitopes are capable of being presented on the cell surface. In HIV-1 infection, naturally occurring HLA class II–restricted altered peptide ligands that fail to stimulate the circulating T lymphocyte repertoire may curtail helper responses at sites where variant viruses predominate.

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Identification of an HIV-1 Nef Peptide That Binds to HLA Class II Antigens

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1994.1557 ◽

1994 ◽

Vol 200 (2) ◽

pp. 1059-1065 ◽

Cited By ~ 30

Author(s):

B.A. Torres ◽

H.M. Johnson

Keyword(s):

Class Ii ◽

Hla Class Ii ◽

Class Ii Antigens ◽

Hiv 1

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HIV-1 Tat mutants in the cysteine-rich region downregulate HLA class II expression in T lymphocytic and macrophage cell lines

European Journal of Immunology ◽

10.1002/1521-4141(200001)30:1<19::aid-immu19>3.0.co;2-9 ◽

2000 ◽

Vol 30 (1) ◽

pp. 19-28 ◽

Cited By ~ 12

Author(s):

Giovanna Tosi ◽

Andrea De Lerma Barbaro ◽

Antonella D'Agostino ◽

Maria Teresa Valle ◽

Anna Maria Megiovanni ◽

...

Keyword(s):

Cell Lines ◽

Class Ii ◽

Hla Class Ii ◽

Macrophage Cell ◽

Rich Region ◽

Hiv 1

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Association of high HIV-1 RNA levels and homozygosity at HLA class II DRB1 in adults coinfected with Mycobacterium tuberculosis in Harare, Zimbabwe

Human Immunology ◽

10.1016/s0198-8859(02)00684-5 ◽

2002 ◽

Vol 63 (11) ◽

pp. 1026-1032 ◽

Cited By ~ 7

Author(s):

Lynn S Zijenah ◽

Wendy E Hartogensis ◽

David A Katzenstein ◽

Ocean Tobaiwa ◽

Junior Mutswangwa ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Class Ii ◽

Hla Class Ii ◽

Hiv 1 ◽

Rna Levels

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Efficient Incorporation of HLA Class II onto Human Immunodeficiency Virus Type 1 Requires Envelope Glycoprotein Packaging

Journal of Virology ◽

10.1128/jvi.74.8.3918-3923.2000 ◽

2000 ◽

Vol 74 (8) ◽

pp. 3918-3923 ◽

Cited By ~ 19

Author(s):

Dexter T. K. Poon ◽

Lori V. Coren ◽

David E. Ott

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Class Ii ◽

Hla Class Ii ◽

Class I ◽

Immunodeficiency Virus ◽

Protein Incorporation ◽

Hiv 1

ABSTRACT HLA class II DR is one of the most abundant cell surface proteins incorporated onto human immunodeficiency virus type 1 (HIV-1) during budding. The mechanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein incorporation, HIV-1 virions, either with or without Env on their surface, were produced from HLA class II-expressing cells and analyzed by whole-virus immunoprecipitation with antisera against HLA class II proteins. HLA class II proteins were detected on virions only when wild-type Env was incorporated, while similar experiments showed that HLA class I proteins were incorporated independent of Env packaging. Therefore, the packaging of HIV-1 Env protein is required for the efficient incorporation of HLA class II but not class I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41TM cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requires Env.

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Faculty Opinions recommendation of HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725645758.793508313 ◽

2015 ◽

Author(s):

Yufei Wang

Keyword(s):

Class Ii ◽

Hla Class Ii ◽

Antibody Responses ◽

Hiv 1

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HLA class II diversity in HIV-1 uninfected individuals from the placebo arm of the RV144 Thai vaccine efficacy trial

Tissue Antigens ◽

10.1111/tan.12507 ◽

2015 ◽

Vol 85 (2) ◽

pp. 117-126 ◽

Cited By ~ 9

Author(s):

K. M. Baldwin ◽

P. K. Ehrenberg ◽

A. Geretz ◽

H. A. Prentice ◽

S. Nitayaphan ◽

...

Keyword(s):

Vaccine Efficacy ◽

Class Ii ◽

Hla Class Ii ◽

Efficacy Trial ◽

Hiv 1

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Quantitation of HLA Class II Protein Incorporated into Human Immunodeficiency Type 1 Virions Purified by Anti-CD45 Immunoaffinity Depletion of Microvesicles

Journal of Virology ◽

10.1128/jvi.77.23.12699-12709.2003 ◽

2003 ◽

Vol 77 (23) ◽

pp. 12699-12709 ◽

Cited By ~ 47

Author(s):

Charles M. Trubey ◽

Elena Chertova ◽

Lori V. Coren ◽

Joanne M. Hilburn ◽

Catherine V. Hixson ◽

...

Keyword(s):

Host Cell ◽

Integral Membrane Protein ◽

Class Ii ◽

Hla Class Ii ◽

Protein Sequencing ◽

Molar Ratio ◽

Host Cell Proteins ◽

The Many ◽

Hiv 1

ABSTRACT Among the many host cell-derived proteins found in human immunodeficiency virus type 1 (HIV-1), HLA class II (HLA-II) appears to be selectively incorporated onto virions and may contribute to mechanisms of indirect imunopathogenesis in HIV infection and AIDS. However, the amount of HLA-II on the surface of HIV-1 particles has not been reliably determined due to contamination of virus preparations by microvesicles containing host cell proteins, including HLA-II. Even rigorous sucrose density centrifugation is unable to completely separate HIV-1 from microvesicles. CD45, a leukocyte integral membrane protein, is found on microvesicles, yet appears to be excluded from HIV-1 particles. Exploiting this observation, we have developed a CD45-based immunoaffinity depletion method for removing CD45-containing microvesicles that yields highly purified preparations of virions. Examination of CD45-depleted HIV-1MN by high-pressure liquid chromatography, protein sequencing, and amino acid analyses determined a molar ratio of HLA-II to Gag of 0.04 to 0.05 in the purified virions, corresponding to an estimated average of 50 to 63 native HLA-II complexes (i.e., a dimer of α and β heterodimers) per virion. These values are approximately 5- to 10-fold lower than those previously determined for other virion preparations that contained microvesicles. Our observations demonstrate the utility of CD45 immunoaffinity-based approaches for producing highly purified retrovirus preparations for applications that would benefit from the use of virus that is essentially free of microvesicles.

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