Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
VIRUS-SPECIFIC CYTOTOXIC T LYMPHOCYTES IN SIMIAN IMMUNODEFICIENCY VIRUS-INFECTED RHESUS MONKEYS
Diss Abstr Int [B]; 52(5):2491 1991. Unique Identifier : AIDSLINE ICDB/92679488 Miller MD; Harvard Univ.
Abstract:
Animal models of acquired immunodeficiency syndrome (AIDS) are needed to facilitate research in disease pathogenesis and vaccine development. Infection of macaque monkeys with the simian immunodeficiency virus (SIV) results in an immunodeficiency syndrome analogous to human AIDS. However, little is known about the cellular immune response to SIV infection, a response which is likely to prove important in both containing the spread of virus and protecting against de novo infection. The research presented herein describes class I major histocompatibility complex (MHC)-restricted, CD8+, cytotoxic T lymphocytes (CTL) which recognize the gag protein of SIV. These gag-specific CTL are observed within the peripheral blood lymphocytes (PBL) of the majority of SIV-infected monkeys. Moreover, the gag-specific CTL from monkeys which express a particular class I MHC molecule, Mamu-A1, recognize an identical 9 amino acid epitope, residues 182-190, within a highly conserved region of the gag protein. CTL clones also recognize the 182-190 gag epitope which demonstrates a highly restricted epitope specificity for the gag protein in Mamu-A1+ monkeys. Mamu-A1 is frequently expressed in rhesus monkeys and has been cloned, sequenced and transfected into a class I MHC-deficient cell line. Mamu-A1 is homologous to HLA-A molecules. Synthetic peptides containing the 9 amino acid gag epitope can bind to transfected Mamu-A1 and be recognized by gag-specific CTL, directly demonstrating that Mamu-A1 presents this peptide to CTL. Mamu-A1+ rhesus monkeys infected with SIV also demonstrate reduced virus load in their PBL and show improved survival after infection. Vaccination of Mamu-A1+ monkeys with a recombinant vaccinia virus expressing the three SIV structural proteins has resulted in a class I MHC-restricted, CD8+ CTL response with the predicted 182-190 gag epitope specificity. The 182-190 peptide epitope of gag is also being used to explore the ability of peptide-based vaccines to induce class I-restricted CTL responses in Mamu-A1+ monkeys. Thus, novel vaccination modalities can now be evaluated for their potential to induce cell-mediated immunity in a well-established animal model of AIDS. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-32004).
Keywords: Animal Epitopes Gene Products, gag/IMMUNOLOGY Histocompatibility Antigens Class I/ANALYSIS Macaca mulatta Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY SIV/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Viral Vaccines/IMMUNOLOGY THESIS 920630
M9261010
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
