NONCLASSICAL BEHAVIOR OF THE THYMUS LEUKEMIA ANTIGEN - PEPTIDE TRANSPORTER-INDEPENDENT EXPRESSION OF A NONCLASSICAL CLASS-I MOLECULE

The thymus leukemia (TL) antigen is a major histocompatibility complex -encoded nonclassical class I molecule. Here we present data demonstra ting that expression of the TL antigen, unlike other class I molecules , is completely independent of the function of the transporter associa ted with antigen processing (TAP). The TL antigen is expressed by tran sfected TAP-2-deficient RMA-S cells when these cells are grown at 37 d egrees C. In transfected RMA cells, the kinetics of arrival of TL anti gen on the cell surface are similar to those of a classical class I mo lecule. The kinetics are not altered in TAP-deficient RMA-S cells, dem onstrating that surface TL expression in TAP-deficient cells is not du e to the stable expression of a few molecules that leak out by a TAP-i ndependent pathway. Soluble TL molecules produced by Drosophila melano gaster cells are highly resistant to thermal denaturation, unlike pept ide-free classical class I molecules synthesized by these insect cells . In addition, these soluble TL molecules are devoid of detectable bou nd peptides. The results demonstrate that the TL antigen is capable of reaching the surface without bound peptide, although acquisition of p eptide or some other ligand through a TAP-independent pathway cannot b e formally excluded. We speculate that the ability of the TL antigen t o reach the cell surface, under conditions in which other class I mole cules do not, may be related to a specialized function of the TL molec ule in the mucosal immune system, and possibly in the stimulation of i ntestinal gamma delta T cells.