CD4 T-Helper Responses to the ALK Protein in Patients with ALK-Positive ALCL.

Anaplstic Lymphoma Kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a favourable prognostic outlook compared to ALK-negative AlCL, possibly as a result of the immune recognition of the ALK protein. We have previously shown the presence of both a cytotoxic T cell and an antibody response to the ALK protein in patients with ALK-positive ALCL. The aim of our present study was to investigate the presence of a CD4 T-helper (Th) response in patients with ALK-positive ALCL and in control individuals. Using the TEPITOPE web-based predicitive search algorithm, three 24-mer promiscuous peptides were identified from the ALK sequence as being potentially immunogenic in the context of MHC class II. A gamma-interferon (γ-IFN) and IL-4 ELISPOT assay was used to detect a T cell response in the peripheral blood cells from patients with ALK-positive and ALK- negative ALCL, as well as healthy controls after 6–11 days of culture with the three peptides. ALK_278–301 and ALK_233–256 were shown to be highly immunogenic in the majority of the ALK-positive patients (see Table). ALK_411–434 was immunogenic to T cells from only one of the ALK-positive patients (Patient 4). Cells from none of the two ALK-negative ALCL patients or the five healthy donors showed any reactivity to the ALK peptides. No response to the control irrelevant peptide was observed in any of the ALCL patients or healthy donors. With the exception of one ALK-positive ALCL patient (Patient 2), no significant IL-4 response was recorded in any of the patients or controls. All of the ALK-positive patients presented antibodies to the ALK protein at time of diagnosis.These findings further demonstrate the immunogenicity of the ALK protein and are suggestive of a Th1 type of immune response to the protein. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond well to chemotherapy.