BlastiMer identifies homologies between the putative epitopes identified by EpiMatrix and any protein sequence on file at GenBank [4]. As a standard practice at EpiVax, any peptide that shares greater than 80% identity with peptides contained in the human proteome is eliminated from consideration. As it turns out, there are many epitopes that are conserved between pathogens and self. Another factor that may play a role in the induction of auto-immunity is what is called “heterologous immunity” or T cell response to epitopes that cross-react with self [11]. The BlastiMer program automates the process of submitting sequences to BLAST engine at NCBI (www.ncbi.nlm.nih.gov/blast). By default, BlastiMer BLASTs sequences against all non-redundant GenBank CDS translations, PDB, SwissProt, PIR, and PRF.

1 De Groot, AS, Jesdale, BM, Szu, E, Schafer, JR. An interactive web site providing MHC ligand predictions: application to HIV research. AIDS Res. and Human Retroviruses. 1997;13: 539-541.

2 Schafer JA, Jesdale BM, George JA, Kouttab NM, De Groot, AS. Prediction of well-conserved HIV-1 ligands using a Matrix-based Algorithm, EpiMatrix. Vaccine. 1998;16(19):1880-1884.

3 Sette A, Sidney J. HLA supertypes and supermotifs: a functional perspective on HLA polymorphism, Current Opinions in Immunology. 1998;10:478-482.

4 Panina-Bordignon P, Tan A, Termijtelen A, Demotz S, Corradin G, Lanzavecchia A. Universally immunogenic T cell epitopes: promiscuous recognition by T cells, European Journal of Immunology 1989 19:2237-2242.

5 De Groot AS, Clerici M, Hosmalin A, Hughes SH, Barnd D, Hendrix CW, Houghten R, Shearer GM, Berzofsky JA. Human Immunodeficiency virus reverse transcriptase T helper epitopes identified in mice and humans: correlation with a cytotoxic T cell epitope, J. Infect Dis, 1991 164:1058-1065.

6 De Groot AS, Rivera DS, McMurry JA, Buus S, Martin W, Identification of Immunogenic HLA-B7 “Achilles’ heel” Epitopes Within Highly Conserved Regions of HIV. Vaccine, 2008;26:3059-3071.

7 De Groot AS, Marcon L, Bishop EA, Rivera D, Kutzler M, Weiner DB, Martin W. HIV vaccine development by computer assisted design: the GAIA vaccine. Vaccine. 2005 Mar 18; 23 [7-18):2136-48.

8 De Groot AS, Ardito M. McClaine E. Moise, L. Martinb W. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-09 Conventional Influenza Vaccine. Vaccine. 2009 Aug 4.Epub ahead of print.

9 Lichterfeld M, Williams KL, Mui SK, Shah SS, Mothe BR, Sette A, Kim A, Johnston MN, Burgett N, Frahm N, Cohen D, Brander C, Rosenberg ES, Walker BD, Altfeld M, Yu XG T cell receptor cross-recognition of an HIV-1 CD8+ T cell epitope presented by closely related alleles from the HLA-A3 superfamily. Int Immunol. 2006 Jul;18(7):1179-88.

10 Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, Addo MM, Feeney ME, Yusim K, Sango K, Brown NV, SenGupta D, Piechocka-Trocha A, Simonis T, Marincola FM, Wurcel AG, Stone DR, Russell CJ, Adolf P, Cohen D, Roach T, StJohn A, Khatri A, Davis K, Mullins J, Goulder PJ, Walker BD, Brander C. Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol. 2004;78:2187-200.

11. Page KR, Scott AL, Manabe YC. The expanding realm of heterologous immunity: friend or foe? Cell Microbiol. 2006 Feb;8(2):185-96.

12. De Groot AS, Bishop EA, Khan B, Lally M, Marcon L, Franco J, Mayer KH, Carpenter CC, Martin W. Engineering immunogenic consensus T helper epitopes for a cross-clade HIV vaccine. Methods. 2004 Dec; 34(4):476-87 Bioinformatics in Vaccine Design.

13. A S. De Groot. Daniel S. Rivera, J. A. McMurry, S. Buus, W. Martin, Identification of Immunogenic HLA-B7 “Achilles’ heel” Epitopes Within Highly Conserved Regions of HIV. Vaccine, 2008 26, 3059—3071.

14. De Groot, A. S. 2006. Immunomics: Discovering New Targets for Vaccine and Therapeutics. Drug Discovery Today. 11:203-209.

15 Leonard Moise, Julie A. McMurry, Soren Buus, Sharon Frey, William D. Martin and Anne S. De Groot. In Silico-Accelerated Identification of Conserved and Immunogenic Variola/Vaccinia T-Cell Epitopes, Submitted to Vaccine (David Weiner, special editor), Published Vaccine. http:/dx.doi.org/10.1016/j.vaccine.2009.06.018 Vaccine. 2009 Jun 24.

16 Gregory SH, Mott S, Phung J, Lee J, Moise L, McMurry JA, Martin W, De Groot AS.Epitope-based vaccination against pneumonic tularemia. Vaccine. 2009 Aug 27;27(39):5299-306. Epub 2009 Jul 17

17 De Groot AS, Berzofsky JA. From genome to vaccine—new immunoinformatics tools for vaccine design. Methods 2004;34: 425–8.

18 Sette A, Sidney J. Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics. 1999;50:201-12.

19 Sette S., Sidney J. 1999 Nine major HLA Class I supertypes account for the vast preponderance of HLA-A and –B polymorphism. Immunogenetics, 50:210-212.

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