Role of HLA-DP in the Presentation of Epitopes from the Truncated Bacterial PE38 Immunotoxin.

Ronit Mazor, Selamawit Addissie, Youjin Jang, Chin-Hsien Tai, Jeremy Rose, Fran Hakim, Ira Pastan

Journal: The AAPS journal 2017;19(1):117-129

PMID: 27796910

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Abstract

Identification of helper T-cell epitopes is important in many fields of medicine. We previously used an experimental approach to identify T-cell epitopes in PE38, a truncated bacterial toxin used in immunotoxins. Here, we evaluated the ability of antibodies to DR, DP, or DQ to block T-cell responses to PE38 epitopes in 36 PBMC samples. We predicted the binding affinities of peptides to DR, DP, and DQ alleles using computational tools and analyzed their ability to predict the T-cell epitopes. We found that HLA-DR is responsible for 65% of the responses, DP 24%, and DQ 4%. One epitope that is presented in 20% of the samples (10/50) is entirely DP restricted and was not predicted to bind to DR or DP reference alleles using binding algorithms. We conclude that DP has an important role in helper T-cell response to PE38.

Address: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, Maryland, 20892-4264, USA.; Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, Maryland, 20892-4264, USA. [email protected].

DOI: 10.1208/s12248-016-9986-y

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MeSH Terms: Algorithms, Alleles, Amino Acid Sequence, Bacterial Toxins, Binding Sites, Cells, Cultured, Epitopes, T-Lymphocyte, Flow Cytometry, Genes, MHC Class II, HLA-DP Antigens, Humans, Immunotoxins, Leukocytes, Mononuclear, Lymphocyte Activation, Peptides