HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products.
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.
Pasquetto
Valerie
V
La Jolla Institute for Allergy and Immunology, San Diego, CA 92109, USA.
Bui
Huynh-Hoa
HH
Giannino
Rielle
R
Banh
Cindy
C
Mirza
Fareed
F
Sidney
John
J
Oseroff
Carla
C
Tscharke
David C
DC
Irvine
Kari
K
Bennink
Jack R
JR
Peters
Bjoern
B
Southwood
Scott
S
Cerundolo
Vincenzo
V
Grey
Howard
H
Yewdell
Jonathan W
JW
Sette
Alessandro
A
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
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