Cross-clade recognition of p55 by cytotoxic T lymphocytes in HIV-1 infection.
OBJECTIVE
To evaluate cross-clade recognition of p55 antigen by cytotoxic T lymphocytes (CTL) in persons infected with diverse clades of HIV-1; to facilitate the development of a CTL-inducing vaccine to prevent transmission of multiple clades of HIV-1.


METHODS
Experiments were designed to evaluate whether persons in Uganda and the United Kingdom, infected with diverse clades of HIV-1, have CTL capable of recognizing and killing autologous target cells infected with recombinant vaccinia viruses (rVV) expressing the Gag protein from A, B, C and D clade HIV-1. The extent of cross-reactivity within such individuals, each infected with characterized virus, might reflect the type of cross-reactive immune response inducible by a monovalent vaccine.


METHODS
Asymptomatic HIV-positive individuals were fully tissue-typed by ARMS (amplification of refractory mutation system) polymerase chain reaction. rVV expressing the Gag protein from identified A, B, C and D viruses were prepared. CTL were cultured and tested for cytolytic activity on autologous rVV-infected or peptide-pulsed B cells.


RESULTS
Ugandan patients had inducible CTL responses recognizing A, B, C and D clade HIV-1 Gag. The majority of UK patients had inducible CTL responses that recognized two or more clades. No patient showed any HIV-2 cross-reactivity. Cross-reactive responses were characterized in three Ugandan patients.


CONCLUSIONS
Most patients tested mounted cross-reactive CTL responses that recognized Gag proteins from clades of HIV-1 other than those with which they were infected.
McAdam
S
S
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Kaleebu
P
P
Krausa
P
P
Goulder
P
P
French
N
N
Collin
B
B
Blanchard
T
T
Whitworth
J
J
McMichael
A
A
Gotch
F
F
D000595:Amino Acid Sequence; D003601:Cytotoxicity Tests, Immunologic; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014454:Uganda; D006113:United Kingdom; D014616:Vaccinia virus / Q000235:genetics
D015683:Gene Products, gag; D016655:HIV Core Protein p24; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D010455:Peptides; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1