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Author(s): Andrew J. McMichael [1]; Sarah L. Rowland-Jones [1] The human immunodeficiency virus (HIV) stimulates strong immune responses by cytotoxic T lymphocytes (CTLs) in infected people [1, 2], despite causing [...]

Author(s): Patrick Champagne [1, 2, 3]; Graham S. Ogg [3, 4]; Abigail S. King [4]; Christian Knabenhans [1]; Kim Ellefsen [1]; Massimo Nobile [1]; Victor Appay [4]; G. Paolo Rizzardi [...]

Recent research has looked at the crystal structure of a complex between CD8-alpha-alpha and the human major histocompatability complex (MHC) molecule HLA-A2, which is linked with peptide. It was found that the binding of CD8 to MHC is consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. This can be concluded from the fact that the binding sites of CD8 and the T-cell antigen receptor to MHC class 1 are separate in spatial terms but need similar orientations of the MHC molecule in relation to the target cell surface.

A mathematical model for the intercalation among cytotoxic T lymphocytes (CTL) and multiple epitopes of a genetically variable pathogen explains that the CTL response is aimed against conserved epitopes. A supreme response is generated against a single epitope by an antigenically homogeneous pathogen population but complex fluctuating responses are induced against multiple epitopes by a heterogeneous pathogen population. The model predicts that disease progression in an HIV-infected person would be slowed if fighting a single epitope and faster if the virus becomes diverse through evolution.

Investigations on variation in HIV-1 gap epitopes that affects cytotoxic T lymphocyte (CTL) recognition reveal that naturally occurring variant forms of p17-3, p24-13 and p24-14 antagonize CTL lines. The effect is noticed when the epitopes are obtained from synthetic peptides and when they are processed from full-length proteins, shown by either recombinant vaccinia constructs or replicating HIV.

The human leukocyte antigen-B53 (HLA-B53) bolsters immunological defenses against the acute form of malaria caused by the parasite Plasmodium falciparum (P. falciparum). Research involving malaria-resistant Africans found that HLA-B53 assisted the cytotoxic T lymphocytes in attacking P. falciparum during the pre-erythrocytic phase of the parasite's life-cycle which occurs in the liver. HLA-B53 may eventually become a key part of a future antimalarial vaccine.

The cytotoxic T lymphocyte (CTL) response is asymmetrical in mice infected with strains of lymphocytic choriomeningitis virus (LCMV) that were either normal (wild type) or mutated at the immunodominant epitopes recognized by the CTL. The CTL responses from mice infected with the mutant virus cross-reacted equally with the mutant and wild-type strains. It is possible that helper T cells, primed by the original virus and subsequently stimulated by the new infection, activate memory B cells specific for the original virus. The response noted may also reflect the extremely strong CTL memory response to LCMV infection.

The Beit Memorial Fellowship scheme, the first specifically to support young UK medical researchers, has made a remarkable contribution to British biomedical science over the past 100 years. John Gurdon's [...]