CD4 T-helper responses to the anaplastic lymphoma kinase (ALK) protein in patients with ALK-positive anaplastic large-cell lymphoma.
We have previously shown both humoral and CTL responses to anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large-cell lymphoma (ALCL). However, because CD4(+) T-helper (Th) cells also play a vital role in developing and maintaining tumor immunity, we investigated the presence of a CD4(+) Th response in ALK-positive ALCL. Using an IFN-gamma ELISPOT assay, we identified two ALK-derived DRB1-restricted 24-mer promiscuous peptides, ALK1(278-301) and ALK2(233-256), as being immunogenic in six ALK-positive ALCL patients but not in two ALK-negative ALCL patients or five normal subjects. A significant interleukin-4 response to the ALK peptides was detected in only one ALK-positive patient. CD4(+) Th cell lines lysed ALK-positive ALCL cell lines in a MHC class II-restricted manner. This first report of a CD4(+) Th response to ALK provides valuable information for developing future immunotherapeutic options for ALK-positive ALCL patients who fail to respond well to conventional therapies.
Ait-Tahar
Kamel
K
Nuffield Department of Clinical Laboratory Sciences, Leukemia Research Fund Immunodiagnostics Unit, John Radcliffe Hospital, Oxford, United Kingdom. kamel.ait-tahar@ndcls.ox.ac.uk
Barnardo
Martin C N
MC
Pulford
Karen
K
D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002478:Cells, Cultured; D002675:Child, Preschool; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases