BASIC SCIENCE

Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57

Gillespie, Geraldine M. A.a; Kaul, Ruperta,c; Dong, Taoa; Yang, Hong-Binga; Rostron, Tima; Bwayo, Job. J.d; Kiama, Peterd; Peto, Timb; Plummer, Francis A.d; McMichael, Andrew J.a; Rowland-Jones, Sarah L.a

Author Information

From the aMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and bNuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK, the cDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Canada and the dDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya.

Requests for reprints to: Dr G. Gillespie, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK.

Received: 3 September 2001;

revised: 23 November 2001; accepted: 8 January 2002.

Sponsorship: this work was supported by grants from the MRC (UK) and the Elizabeth Glaser Paediatric AIDS Foundation. SRJ is an Elizabeth Glaser Scientist of the Paediatric AIDS Foundation.

AIDS 16(7):p 961-972, May 3, 2002.

Abstract

Objectives 

To determine whether CD8 T lymphocytes from HIV-1-infected patients expressing B*5701 and B*5703 show broad cross-reactivity against different variants of a conserved p24 epitope, which might account for the good prognosis of HIV-1-infected individuals with HLA-B*57.

Design 

B*5701+ and B*5703+ were recruited from Nairobi, Kenya and from Oxford, UK. All patients had been HIV positive for at least 8 years and could be categorized as slow progressors.

Methods 

CD8 cytotoxic T cell clones were generated from B*5701+ and B*5703+ donors and tested for their ability to recognize clade variants of an index p24 epitope in standard cytolytic assays. Cross-reactive responses in freshly isolated peripheral blood mononuclear cells (PBMC) were assessed by interferon-γ (IFNγ) production and tetramer binding.

Results 

Broad cross-clade reactivity for both cytolysis and tetramer binding was observed in CD8 T cell clones from patients harbouring the index epitope sequence. Patterns of cross-reactivity were similar in freshly isolated PBMC but varied between individuals in terms of strength and breath of responses generated. One common variant induced an unusual response with tetramer binding but often failed to induce IFNγ production, and another was a weak stimulator of both IFNγ and cytolytic activity.

Conclusion 

B*5701+ and B5703+ donors demonstrate broad functional cross-reactivity to both common and rare variants of a dominant p24 epitope, which could be relevant to the association of B*57 alleles with slow progression to AIDS.

© 2002 Lippincott Williams & Wilkins, Inc.

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