Cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV p17 GAG:77-85 epitopes in HIV-infected and uninfected individuals

被引:35
作者
Paula M Acierno
Danforth A Newton
Edwin A Brown
Lou Anne Maes
John E Baatz
Sebastiano Gattoni-Celli
机构
[1] Department of Radiation Oncology, Medical University of South Carolina, Charleston
[2] Department of Medicine, Medical University of South Carolina, Charleston
[3] Department of Pathology, Medical University of South Carolina, Charleston
[4] Department of Pediatrics, Medical University of South Carolina, Charleston
[5] Dept. of Microbiology/Immunology, Medical University of South Carolina, Charleston
关键词
Human Immunodeficiency Virus; Influenza; Seronegative Donor;
D O I
10.1186/1479-5876-1-3
中图分类号
学科分类号
摘要
Background. The matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities which may have evolutionary and biological significance. These similarities led us to hypothesize the existence of cross-reactivity between HLA- A2-restricted FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes. Methods. The hypothesis that these two epitopes are cross-reactive was tested by determining the presence and extent of FLU/GAG immune cross-reactivity in lymphocytes from HIV-seropositive and seronegative HLA-A2+ donors by cytotoxicity assays and tetramer analyses. Moreover, the molecular basis for FLU/GAG cross-reactivity in HIV-seropositive and seronegative donors was studied by comparing lymphocyte-derived cDNA sequences corresponding to the TCR-β variable regions, in order to determine whether stimulation of lymphocytes with either peptide results in the expansion of identical T-cell clonotypes. Results. Here, we report evidence of cross-reactivity between FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes following in vitro stimulation of PBMC derived from either HIV-seropositive or seronegative HLA-A2+ donors as determined by cytotoxicity assays, tetramer analyses, and molecular clonotyping. Conclusion. These results suggest that immunity to the matrix protein of the influenza virus may drive a specific immune response to an HLA-A2-restricted HIV gag epitope in HIV-infected and uninfected donors vaccinated against influenza. © 2003 Acierno et al; licensee BioMed Central Ltd.
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共 28 条
[1]  
Harris A., Sha B., Luo M., Structural similarities between influenza virus matrix protein M1 and human immunodeficiency virus matrix and capsid proteins: An evolutionary link between negative-stranded RNA viruses and retroviruses, J. Gen. Virol., 80, pp. 863-869, (1999)
[2]  
Bodmer H., Ogg G., Gotch F., McMichael A., Anti-HLA-A2 antibody-enhancement of peptide association with HLA-A2 as detected by cytotoxic T lymphocytes, Nature, 342, pp. 443-446, (1989)
[3]  
Tsomides T.J., Aldovini A., Johnson R.P., Walker B.D., Young R.A., Eisen H.N., Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1, J. Exp. Med., 180, pp. 1283-1293, (1994)
[4]  
Altman J.D., Moss P.A., Goulder P.J., Barouch D.H., McHeyzer-Williams M.G., Bell J.I., McMichael A.J., Davis M.M., Phenotypic analysis of antigen-specific T lymphocytes, Science, 274, pp. 94-96, (1996)
[5]  
Salgaller M.L., Marincola F.M., Cormier J.N., Rosenberg S.A., Immunization against epitopes in the human melanoma antigen gpl00 following patient immunization with synthetic peptides, Cancer Res., 56, pp. 4749-4757, (1996)
[6]  
Salter R.D., Cresswell P., Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell 879 hybrid, EMBO J., 5, pp. 943-949, (1986)
[7]  
Schrama D., Andersen M.H., Terheyden P., Schroder L., Otergaard Pedersen L., thor Straten P., Becker J.C., Oligoclonal T-cell receptor usage of melanocyte differentiation antigen-reactive T cells in stage IV melanoma patients, Cancer Res., 61, pp. 493-496, (2001)
[8]  
thor Straten P., Barfoed A., Seremet T., Saeterdal I., Zeuthen J., Guldberg P., Detection and characterization of αβ-T-cell clonality by denaturing gradient gel electrophoresis (DGGE), BioTech, 25, pp. 244-250, (1998)
[9]  
Grene E., Newton D.A., Brown E.A., Berzofsky J.A., Gattoni-Celli S., Shearer G.M., Semi-allogeneic cell hybrids stimulate HIV-1 envelope-specific cytotoxic T lymphocytes, AIDS, 14, pp. 1497-1506, (2000)
[10]  
Myers R.M., Maniatis T., Lerman L.S., Detection and localization of single base changes by denaturing gradient gel electrophoresis, Meth. Enzymol., 155, pp. 501-527, (1987)