Absence of Unexpected H-2 Alloantigens on a Murine Lymphoma

Abstract

The chemical nature of the structures recognized on target cell membranes by cytotoxic lymphocytes (CTL) remains unclear. One hypothesis suggests that new H-2 alloantigens may be de-repressed as a consequence of viral infection or transformation. We have attempted to detect the appearance of any “foreign” H-2 antigens on the Moloney virus-induced lymphoma LSTRA (H-2d), by analyzing 125I-labeled LSTRA membranes from detergent-solubilized cells, immunoprecipitated with anti-H-2 or anti-β2 microglobulin sera.We have previously demonstrated that LSTRA bears H-2Dd and H-2Kd antigens that are indistinguishable from BALB/c antigens in their size, isoelectric properties, and antigenicity. We now extend these studies by showing that: 1) All molecules precipitated by anti-β  2 microglobulin sera (other than β  2 microglobulin) could be removed by pretreatment with anti-H-2d sera. 2) LSTRA cells were specifically examined for H-2d antigens (reported by others to be on LSTRA cells); no such molecules were detected. 3) H-2 molecules precipitated from 125I-LSTRA membrane with anti-β  2 sera were indistinguishable from those obtained from 125I-BALB/c membrane in their appearance on two-dimensional gels, ruling out modifications of existing H-2 molecules or substitutions for them in association with β-2.We also noted that three different xenoantisera to β-2 microglobulins precipitated selected populations of H-2-β-2 dimers—either H-2Dd + β-2, or H-2Kd + β-2, or both. This phenomenon might be explained by true heterogeneity of β-2 microglobulins, or by selective expression of different determinants on a homogeneous population of β-2 molecules as a result of their differential association with H-2Kd and H-2Dd glycoproteins.This publication expands our previous work to characterize H-2 antigens on the membrane of LSTRA cells that can serve as targets for H-2 restricted lysis by immune CTL. The data presented here and in our previous work allow exclusion of certain models of the membrane structures that are recognized on the target cell during cell-mediated lysis.