Title

Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS

Authors

Xiaojiang Gao, National Cancer Institute at Frederick
George W. Nelson, National Cancer Institute at Frederick
Peter Karacki, Johns Hopkins Medical Institutions
Maureen P. Martin, National Cancer Institute at Frederick
John Phair, Northwestern University Medical School
Richard A. Kaslow, University of Alabama - Birmingham
James J. Goedert, National Cancer Institute at Bethesda
Susan Buchbinder, San Francisco Department of Public Health
Keith Hoots, University of Texas Health Science Center at Houston
David Vlahov, Johns Hopkins School of Hygiene and Public Health
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Mary Carrington, National Cancer Institute at Frederick

Document Type

Article

Publication Date

5-31-2001

Publication Title

New England Journal of Medicine

ISSN

0028-4793

Volume

344

Issue/No.

22

First Page

1668

Last Page

1675

Abstract

Background From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLAB* 35 subtypes with different peptide-binding specificities.

Results HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLAB* 3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLAB* 35-Px alleles, some of which differ from HLA-B*35- PY alleles by only one amino acid residue.

Conclusions This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1.

Comments

©2001 Massachusetts Medical Society

Additional Comments

National Cancer Institute contract #: NO-1-CO-56000; National Institutes of Health contract #: R01-AI-41951

NSUWorks Citation

Gao, Xiaojiang; George W. Nelson; Peter Karacki; Maureen P. Martin; John Phair; Richard A. Kaslow; James J. Goedert; Susan Buchbinder; Keith Hoots; David Vlahov; Stephen J. O'Brien; and Mary Carrington. 2001. "Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS." New England Journal of Medicine 344, (22): 1668-1675. https://nsuworks.nova.edu/cnso_bio_facarticles/794

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015