Journal Article

Conserved HIV-1 Epitopes Continuously Elicit Subdominant Cytotoxic T-Lymphocyte Responses

Yi Liu, John McNevin, Morgane Rolland, Hong Zhao, Wenjie Deng, Janine Maenza, Claire E. Stevens, Ann C. Collier, M. Juliana McElrath and James I. Mullins

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 200, issue 12, pages 1825-1833
Published in print December 2009 | ISSN: 0022-1899
Published online December 2009 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1086/648401
Conserved HIV-1 Epitopes Continuously Elicit Subdominant Cytotoxic T-Lymphocyte Responses

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BackgroundThe epitope specificities and antiviral activities of class I HLA-restricted CD8+ T cells, especially those induced during human immunodeficiency virus type 1 (HIV-1) primary infection, are important considerations in designing HIV-1 vaccines. Conserved epitopes may be more commonly and persistently recognized than variable epitopes, as they may be more likely to be present in infecting viruses. However, some studies have shown preferential or similar targeting of variable versus conserved epitopes during primary infection

MethodsWe analyzed cytotoxic T-lymphocyte (CTL) responses toward predefined conserved and variable epitopes in 45 subjects during primary (n=34) and/or chronic infection (n=16)

ResultsConserved and variable CTL epitopes were recognized with similar probabilities, whereas conserved epitopes generally elicited subdominant responses during both primary and chronic infection. During primary infection, CTL responses against Gag versus responses against Env and variable epitopes tended to be associated with lower and higher viral loads, respectively. During chronic infection, Env-specific responses tended to be associated with lower CD4+ cell counts

ConclusionsSubdominant CTL recognition of conserved HIV-1 epitopes commonly occurs from the primary through chronic stages of HIV-1 infection. These findings underscore the challenge in designing T cell–based vaccines that can induce immunodominant CTL responses to conserved HIV-1 regions

Journal Article.  5141 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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