title: HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products.
abstract: In virus models explored in detail in mice, CTL typically focus on a few immunodominant determinants. In this study we use a multipronged approach to understand the diversity of CTL responses to vaccinia virus, a prototypic poxvirus with a genome approximately 20-fold larger than that of the model RNA viruses typically studied in mice. Based on predictive computational algorithms for peptide binding to HLA supertypes, we synthesized a panel of 2889 peptides to begin to create an immunomic map of human CTL responses to poxviruses. Using this panel in conjunction with CTLs from vaccinia virus-infected HLA transgenic mice, we identified 14 HLA-A*0201-, 4 HLA-A*1101-, and 3 HLA-B*0702-restricted CD8(+) T cell determinants distributed over 20 distinct proteins. These peptides were capable of binding one or multiple A2, A3, and B7 supertype molecules with affinities typical of viral determinants. Surprisingly, many of the viral proteins recognized are predicted to be late gene products, in addition to the early intermediate gene products expected. Nearly all of the determinants identified have identical counterparts encoded by modified vaccinia virus Ankara as well as variola virus, the agent of smallpox. These findings have implications for the design of new smallpox vaccines and the understanding of immune responses to large DNA viruses in general.
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, CA 92109, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Pasquetto
authors.forename: Huynh-Hoa
authors.initials: HH
authors.lastname: Bui
authors.forename: Rielle
authors.initials: R
authors.lastname: Giannino
authors.forename: Cindy
authors.initials: C
authors.lastname: Banh
authors.forename: Fareed
authors.initials: F
authors.lastname: Mirza
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Carla
authors.initials: C
authors.lastname: Oseroff
authors.forename: David C
authors.initials: DC
authors.lastname: Tscharke
authors.forename: Kari
authors.initials: K
authors.lastname: Irvine
authors.forename: Jack R
authors.initials: JR
authors.lastname: Bennink
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Scott
authors.initials: S
authors.lastname: Southwood
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Howard
authors.initials: H
authors.lastname: Grey
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D015793:HLA-B7 Antigen; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011237:Predictive Value of Tests; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D014764:Viral Proteins