Thymus-leukemia antigen (TL) as a major histocompatibility complex (MHC) class Ib molecule and tumor-specific antigen.

Abstract

Mouse thymus-leukemia antigens (TL) belong to the family of major histocompatibility complex (MHC) class Ib antigens and have a unique mode of expression, i.e., in contrast to other MHC class Ib or Ia antigens, they are found restricted to the intestines in all mouse strains, but also in the thymus of certain strains (TL(+) strains). Nevertheless, a proportion of T lymphomas/leukemias in strains that do not express TL in the thymus (TL(-) strains) feature TL as a tumor antigen. TL was originally defined serologically, but subsequently we have succeeded in generating T cell receptor (TCR) and cytotoxic T lymphocytes (CTL) recognizing TL. By use of TL tetramers free from peptides and transfectants expressing various TL/H-2 chimeric molecules, we have been able to show that TL-specific CTL recognize the alpha1/alpha2 domain of TL without any additional antigen molecules. We previously reported that one of TL's functions in the thymus is positive selection of TCR CTL. Recent studies with TL tetramers revealed that they can bind to normal intestinal intraepithelial lymphocytes (iIEL) and thymocytes in a CD8-dependent, but TCR/CD3-independent manner, while their binding to TL-specific CTL is TCR/CD3- and CD8-dependent. The possible significance of these findings in relation to the roles of TL in the intestines is discussed. We have long been interested in TL as a model tumor antigen which shares characteristics with human differentiation tumor antigens, and we have demonstrated that growth of TL(+) lymphoma cells in vivo is suppressed by immunization with TL(+) skin or dendritic cells (DC) from TL transgenic mice. In addition, anti-tumor effects against TL(+) T lymphomas were obtained by adoptive transfer of TL tetramer strongly-positive TL-specific CTLs.