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Class I Peptides (class + i_peptide)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Extensive HLA class I allele promiscuity among viral CTL epitopes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007
Nicole Frahm
Abstract Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. [source]

Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapy

PROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2007
Iņaki Alvarez
Abstract HLA class I molecules present peptides on the cell surface to CD8+ T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients. [source]

The Indirect Alloresponse Impairs the Induction but Not Maintenance of Tolerance to MHC Class I-Disparate Allografts

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
M. J. Weiss
We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney,heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney,heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance. [source]

Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70) can function to eradicate tumors

CANCER SCIENCE, Issue 5 2008
Shusaku Mizukami
Vaccination with heat shock proteins (HSP) protects mice from challenge with the tumor from which the HSP were isolated. The antigenicity of HSP vaccination is thought to result from HSP-associated endogenous major histocompatibility complex class I peptides or their precursors. The vaccination effect can be achieved in an adjuvant-free manner and is mediated by CD8+ T cells, indicating that HSP can act as a natural adjuvant and cross-prime T cells in vivo. We previously devised a recombinant vaccine composed of a CD8+ T cell epitope fused to the carboxyl-terminus of hsc70 and demonstrated efficient generation of antigen-specific cytotoxic T lymphocyte (CTL) after vaccination with a few micrograms of the hsc70-CTL epitope fusion protein. The present study aimed to determine if the fusion protein vaccine could control tumor growth in vivo and whether simultaneous fusion of a CD4+ T cell epitope to the amino terminus of the hsc70-CTL epitope would be a more potent vaccine compared to the CTL epitope alone. Ovalbumin (OVA),derived 8 mer peptide, OVA257-264, and 16mer peptide, OVA265-280, were used as CD8+ and CD4+ T cell epitopes, respectively. Vaccination with hsc70-OVA257-264 generated peptide specific CTL more effectively than a peptide plus incomplete Freund's adjuvant combination, and suppressed growth of OVA expressing EL4 (E.G7) and B16 melanoma tumor cells. Addition of OVA265-280 to the amino-terminus of hsc70-OVA257-264 (OVA265-280 -hsc70-OVA257-264) enhanced the generation of the OVA257-264 -specific CTL population, leading to better eradication of MO5 lung metastasis compared to hsc70-OVA257-264. Our results suggest that fusion of both CD4+ and CD8+ T cell epitopes to hsc70 enhances tumor immunity beyond the effect of the CD8+ T cell epitope alone. (Cancer Sci 2008; 99: 1008,1015) [source]