Abstract
Three moderately to broadly recognized equine infectious anemia virus (EIAV) peptides that contained helper T-lymphocyte (Th) 1 epitopes were previously identified. Although lipopeptide immunization was only weakly immunostimulatory in a preliminary study, as measured by T-lymphocyte proliferation responses, it was of interest to define additional broadly recognized Th1 epitopes to include in future immunization trials. Using broadly cross-reactive and conserved Th epitopes known in the related human immunodeficiency virus-1 (HIV-1) and binding motifs defined in human leukocyte antigen DR molecules as guides, this work identified three new peptides containing Th1 epitopes recognized by 60–75% of EIAV infected horses. The observed similarity across species of major histocompatibility complex (MHC) class II binding motifs and the conservation of Th peptides between related viruses should allow easier targeting of Th epitope regions in less well characterized pathogens and/or in species whose MHC class II molecules are poorly defined.
This is a preview of subscription content, log in via an institution to check access.
References
Albright-Fraser DG, Reid R, Gerber V, Bailey E (1996) Polymorphism of DRA among equids. Immunogenetics 43:315–317, erratum Immunogenetics 44:487
Allen G, Yeargan M, Costa LRR, Cross R (1995) Major histocompatibility complex class I-restricted cytotoxic T lymphocyte responses in horses infected with equine herpesvirus 1. J Virol 69:606–612
Arnold PY, La Gruta NL, Miller T, Vignali KM, Adams PS, Woodland DL, Vignali DAA (2002) The majority of immunogenic epitopes generate CD4+ T cells that are dependent on MHC class II-bound peptide-flanking residues. J Immunol 169:739–749
Bernoco D, Antczak DF, Bailey E, Bell K, Bull RW, Byrns G, Guerin G, Lazary S, McClure J, Templeton J, Varewyck H (1987) Joint report of the fourth international workshop on lymphocyte alloantigens of the horse, Lexington, Kentucky, 12–22 October 1985. Anim Genet 18:81–94
Cardin RD, Brooks JW, Sarawar SR, Doherty PC (1996) Progressive loss of CD8+ T cell-mediated control of a γ-herpesvirus in the absence of CD4+ T cells. J Exp Med 184:863–871
de Quiros JC, Shupert WL, McNeil AC, Gea-Banacloche JC, Flanigan M, Savage A, Martino L, Weiskopf EE, Imamichi H, Zhang YM, Adelsburger J, Stevens R, Murphy PM, Zimmerman PA, Hallahan CW, Davey RT Jr, Connors M (2000) Resistance to replication of human immunodeficiency virus challenge in SCID-Hu mice engrafted with peripheral blood mononuclear cells of nonprogressors is mediated by CD8(+) T cells and associated with a proliferative response to p24 antigen. J Virol 74:2023–2028
Dzuris JL, Sidney J, Horton H, Correa R, Carter D, Chesnut RW, Watkins DI, Sette A (2001) Molecular determinants of peptide binding to two common rhesus macaque major histocompatibility complex class II molecules. J Virol 75:10958–10968
Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 35:161–214
Fraser DG, Bailey E (1998) Polymorphism and multiple loci for the horse DQA gene. Immunogenetics 47:487–490
Fraser DG, Oaks JL, Brown WC, McGuire TC (2002) Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus. Immunology 105:295–305
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC (1997) Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. J Virol 71:3840–3852
Hammond SA, Cook SJ, Falo LD Jr, Issel CJ, Montelaro RC (1999) A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus. Virology 254:37–49
Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC (2000) Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids. J Virol 74:3112–3121
Heeney JL (2002) The critical role of CD4+ T-cell help in immunity to HIV. Vaccine 20:1961–1963
Hunziker L, Klenerman P, Zinkernagel RM, Ehl S (2002) Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells. Eur J Immunol 32:374–382
Imami N, Pires A, Hardy G, Wilson J, Gazzard B, Gotch F (2002) A balanced type 1/type 2 response is associated with long-term nonprogressive human immunodeficiency virus type 1 infection. J Virol 76:9011–9023
Kono Y (1969) Viremia and immunological responses in horses infected with equine infectious anemia virus. Natl Inst Anim Health Q (Tokyo) 9:1–9
Matloubian M, Concepcion RJ, Ahmed R (1994) CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol 68:8056–8063
McGuire TC, Crawford TB, Henson JB (1971) Immunofluorescent localization of equine infectious anemia virus in tissue. Am J Pathol 62:283–294
McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE (1994) Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins. J Virol 68:1459–1467
Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC (2003) Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus. Virology 313:537–552
Oaks JL, Ulibarri C, Crawford TB (1999) Endothelial cell infection in vivo by equine infectious anaemia virus. J Gen Virol 80:2393–2397
O'Rourke K, Perryman LE, McGuire TC (1988) Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. J Gen Virol 69: 667–674
Pearson JE, Coggins L (1979) Protocol for the immunodiffusion (Coggins) test for equine infectious anemia. Proc Am Assoc Vet Lab Diagn 22:449–462
Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC (1998) Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement. Virology 245:151–162
Ridgely SL, Zhang B, McGuire TC (2003) Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge. Vaccine 21:491–506
Southwood S, Sidney J, Kondo A, del Guercio M-F, Appella E, Hoffman S, Kubo RT, Chesnut RW, Grey HM, Sette A (1998) Several Common HLA-DR types share largely overlapping peptide binding repertoires. J Immunol 160:3363–3373
Stephens RM, Casey JW, Rice NR (1986) Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science 231:589–594
Terasaki PI, Bernoco D, Park MS, Ozturk G, Iwaki Y (1978) Microdroplet testing for HLA-A, -B, -C and -D antigens. The Philip Levine Award Lecture. Am J Clin Pathol 69:103–120
Vitiello A, Ishioka G, Grey HM, Rose R, Farness P, LaFond R, Yuan L, Chisari FV, Furze J, Bartholomeuz R, Chesnut RW (1995) Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. J Clin Invest 95:341–349
Wilson CC, Palmer B, Southwood S, Sidney J, Higashimoto Y, Appella E, Chesnut R, Sette A, Livingston BD (2001) Identification and antigenicity of broadly cross-reactive and conserved human immunodeficiency virus type 1-derived helper T-lymphocyte epitopes. J Virol 75:4195–4207
Acknowledgements
The authors thank Emma Karel and Andra Edwards for help with the horses, Matt Littke and Steve Leib for technical assistance, and Gerhard Munske for peptide and lipopeptide syntheses. This work was supported by U.S. Public Health Services' Individual National Research Service Award AI10528 (to D.G.F.), and Research Grants AI24291 and AI47660 (to T.C.M.). All experiments described herein comply with the current laws of the United States of America.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fraser, D.G., Mealey, R.H. & McGuire, T.C. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. Immunogenetics 55, 508–514 (2003). https://doi.org/10.1007/s00251-003-0600-y
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-003-0600-y