Specific human cellular immunity to bcr-abl oncogene-derived peptides Journal Article

  

Authors:	Bocchia, M.; Korontsvit, T.; Xu, Q.; Mackinnon, S.; Yang, S. Y.; Sette, A.; Scheinberg, D. A.
Article Title:	Specific human cellular immunity to bcr-abl oncogene-derived peptides
Abstract:	Chronic myelogenous leukemia (CML) cells are characterized by a t(9;22) translocation, which can encode one of two chimeric P210 bcr-abl fusion proteins, comprising products of either the b2a2 or the b3a2 exon junction. The junctional sequences represent potentially immunogenic tumor-specific antigens. Despite their intracellular location, the fusion proteins might be recognized immunologically by T lymphocytes if peptides, derived from these unique sequences, are capable of presentation by the major histocompatibility complex molecules. We previously found that four peptides, 9 to 11 amino acids long, spanning the b3a2 CML breakpoint bind with high or intermediate affinity to purified HLA class I molecules A3, A11, B8, or both A3 and A11. We tested the ability of these peptides to elicit specific class I restricted cytotoxic T lymphocytes (CTLs) in vitro in HLA-matched healthy donors. In addition, a longer b3a2 CML-breakpoint-derived peptide, 25 aminoacids in length (b3a2-25), was studied for its ability to induce peptide-specific, class II-mediated, T-cell proliferation. In four of four HLA-A3 donors tested, CML-A3/A11-peptide specific CTLs were induced that killed an allogeneic HLA-A3-matched peptide pulsed leukemia cell line. In two of three HLA-A3 donors, the CML-A3/A11 peptide was able to induce killing of autologous and allogeneic HLA-matched peptide-pulsed peripheral blood mononuclear cells (PBMC). CML-A3 peptide induced peptide specific CTLs in one of the four HLA A3 donors tested. No killing was observed in two HLA-B8 and two HLA-A11 donors. PBMC from seven donors were also tested for anti b3a2-25 peptide proliferation in a thymidine incorporation assay. Specific proliferation was detected in three donors, all of the HLA-DR11 haplotype. These data represent the first evidence of a cytolytic human immune response against CML bcr-abl oncogene-derived peptides and provide a rationale for developing peptide-based vaccines for this disease.
Keywords:	human cell; proto-oncogene proteins; lymphocyte proliferation; cell division; tumor cells, cultured; chronic myeloid leukemia; tumor antigen; antigen presentation; lymphocyte activation; cellular immunity; amino acid sequence; molecular sequence data; antigens, neoplasm; recombinant fusion proteins; antigen specificity; oncogene proteins; hla dr antigen; t-lymphocytes, cytotoxic; hla antigen class 1; peptides; protein-tyrosine kinases; host resistance; major histocompatibility complex; hla b antigen; hla typing; t lymphocyte activation; immunity, cellular; chromosome translocation 21; proto-oncogene proteins c-abl; hla a3 antigen; humans; human; priority journal; article; chromosome translocation 9; proto-oncogene proteins c-bcr
Journal Title:	Blood
Volume:	87
Issue:	9
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	1996-05-01
Start Page:	3587
End Page:	3592
Language:	English
PUBMED:	8611681
PROVIDER:	scopus
DOI:	10.1182/blood.V87.9.3587.bloodjournal8793587
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029870222&partnerID=40&md5=76fb1f6decccce73db71bacba3afcb40
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/118719