The effects of natural altered peptide ligands on the whole blood cytotoxic T lymphocyte response to human immunodeficiency virus

European Journal of Immunology
P KlenermanA J McMichael

Abstract

Cytotoxic T lymphocytes (CTL) directed against human immunodeficiency virus (HIV)-1 are detectable in the majority of infected individuals, and their early appearance as the initial viremia is suppressed is thought to represent a potent antiviral response. Variation which arises in CTL epitopes can affect recognition by CTL, and we have observed previously that variant epitopes in HIV-1 gag which arise in HIV-1-seropositive donors may act as T cell receptor (TCR) antagonists of their own CTL (Klenerman et al., Nature 1994, 369: 403). The most important question arising from these observations is the extent of these immune escape mechanisms in vivo. Here we show that fresh, uncultured lymphocytes taken directly from HIV-1-infected patients are susceptible to TCR antagonism by variants present within their own virus. In contrast to HLA Class II-restricted T cell responses, where anergy may be induced, we find that in vitro, natural variants may stimulate and sustain growth of CTL. These CTL lines retain lytic specificity exclusively for the original peptide. If this represents events in vivo, natural HIV altered peptide ligands (APL) have the capacity to inhibit the range of CTL directed against an epitope, not simply those clone...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·B D WalkerR T Schooley
Sep 1, 1966·The Journal of Experimental Medicine· Fazekas de St Groth, R G Webster
Sep 1, 1966·The Journal of Experimental Medicine· Fazekas de St Groth, R G Webster
Jun 2, 1994·Nature·P M Allen, R M Zinkernagel
Sep 1, 1994·The Journal of Experimental Medicine·R A Koup
Apr 1, 1995·Journal of Virology·D Moskophidis, R M Zinkernagel
Oct 1, 1994·The Journal of Experimental Medicine·J Sloan-LancasterP M Allen
Oct 1, 1994·Immunology Today·H KöhlerP L Nara
Jun 30, 1994·Nature·S C JamesonM J Bevan
Jan 1, 1994·Annual Review of Immunology·A SetteH M Grey
Aug 11, 1994·Nature·R A Koup, D D Ho
Jan 14, 1994·Cell·K A HogquistF R Carbone

❮ Previous
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Citations

Apr 28, 2004·Microbes and Infection·Kathleen L Collins
Aug 1, 1996·Current Opinion in Immunology·B AutranG Haas
May 3, 2002·Clinical and Experimental Immunology·S WardP Klenerman
Nov 17, 1998·The Journal of Experimental Medicine·G C HarcourtR E Phillips
Apr 3, 1999·Viral Immunology·L Menéndez-AriasE Domingo
Mar 11, 1998·Proceedings. Biological Sciences·D WodarzM A Nowak
May 7, 1998·Proceedings. Biological Sciences·N J Burroughs, D A Rand
Jan 1, 1999·Proceedings. Biological Sciences·D Wodarz, M A Nowak
May 17, 2013·Proceedings. Biological Sciences·Duncan PalmerGil McVean
Jul 10, 1999·Immunological Reviews·K L Collins, D Baltimore
Jul 10, 1999·Immunological Reviews·D Wodarz, M A Nowak
Nov 27, 2004·Journal of Virology·David H O'ConnorDavid I Watkins
Jan 1, 1997·Annual Review of Immunology·A J McMichael, R E Phillips
Apr 18, 2013·PloS One·Yongli HuAsif M Khan
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M A PurbhooR E Phillips
Dec 11, 1997·Lancet·C R Bangham, R E Phillips
Jun 18, 1998·Cell·A McMichael
Aug 11, 1998·Nature·A J McMichael
Mar 9, 2000·Journal of Acquired Immune Deficiency Syndromes : JAIDS·D FenoglioF Manca
Jan 8, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sean C EliasSimon J Draper
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa K McNeil, Brian D Evavold
Dec 13, 2005·Clinical Science·Rebekah L Puls, Sean Emery
Dec 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Palanee AmmaranondAnthony D Kelleher
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Margaret E FeeneyPhilip J R Goulder
Nov 13, 2001·International Journal of Experimental Pathology·M LucasP Klenerman
May 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·R KubotaS Jacobson
Nov 24, 1995·Science·U C MeierR Phillips

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