Premium
A novel immunogenic CS 1‐specific peptide inducing antigen‐specific cytotoxic T lymphocytes targeting multiple myeloma
Author(s) -
Bae Jooeun,
Song Weihua,
Smith Robert,
Daley John,
Tai YuTzu,
Anderson Kenneth C.,
Munshi Nikhil C.
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09111.x
Subject(s) - ctl* , cytotoxic t cell , degranulation , antigen , cd8 , biology , immunology , microbiology and biotechnology , t cell , immune system , in vitro , biochemistry , receptor
Summary The CS 1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma ( MM ). This study aimed to identify HLA ‐ A 2 + immunogenic peptides from the CS 1 antigen, which induce peptide‐specific cytotoxic T lymphocytes ( CTL ) against HLA ‐ A 2 + MM cells. We identified a novel immunogenic HLA ‐ A 2‐specific CS 1 239‐247 ( SLFVLGLFL ) peptide, which induced CS 1‐specific CTL ( CS 1‐ CTL ) to MM cells. The CS 1‐ CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL . CS 1 239‐247 peptide‐specific CD 8 + T cells were detected by Dimer X analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA ‐A2‐restricted and antigen‐specific cytotoxicity, proliferation, degranulation and γ‐interferon ( IFN ‐γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset ( CD 45 RO + CCR 7 − / CD 3 + CD 8 + ) within CS 1‐ CTL showed a higher level of CD 107a degranulation and IFN ‐γ production as compared to effector cells ( CD 45 RO − CCR 7 − / CD 3 + CD 8 + ) against HLA ‐ A 2 + primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA ‐ A 2‐specific CS 1 239‐247 peptide capable of inducing antigen‐specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.