Synthesis and cell surface display of class II determinants by long‐term propagated rat T line cells

Abstract

We have investigated the capacity of the encephalitogenic BS rat T cell line bs 83 and its variant clone bs 83.III.C6 to synthesize and express RT1.B-specific class II molecule subsets defined by monoclonal antibodies (mAb) MRC-OX6 and MRC-OX3. Earlier studies had indicated that mAb MRC-OX6 recognizes three distinct molecular species: an immature oligomeric polypeptide chain complex comprised of the polymorphic subunits alpha, beta and the invariant proteins of the gamma group; a biosynthetic intermediate composed of post-translationally modified alpha, beta and gamma chain (denoted p35) and a fully glycosylated alpha, beta two-chain complex derived from the plasma membrane. MRC-OX3 was shown to recognize a serologically distinct alpha, beta two-chain complex that coexists with the MRC-OX6-specific heterodimer at the cell surface. Here we show that premutant bs 83 cells were unable to synthesize class II molecules of either set. In contrast endogeneous synthesis by mutant cells of MRC-OX6-specific molecules was demonstrated. Unlike control spleen cells variant cells failed to synthesize the mature MRC-OX3-reactive class II subset. Instead a three-polypeptide chain complex comprised of the terminally glycosylated subunits alpha, beta and invariant chain p35 was present at the cell surface. This complex appears to represent the preserved biosynthetic intermediate that failed to release invariant chain p35 upon its transit into the plasma membrane. These latter observations support our notion of gamma chain-induced epitope diversification during post-translational maturation of RT1.B-specific class II molecules.

Positional Identification ofRT1-B(HLA-DQ) as Susceptibility Locus for Autoimmune Arthritis

“…These experiments also showed that intact IgG directed to either RT1-B or RT1-D had an immense suppressive effect on the arthritis development, which we assume is a consequence of Abmediated depletion of MHC-II + cells during T cell priming. The most plausible explanation for the suppression of arthritis in rats treated with OX6 and OX17 IgG is therefore that disease-initiating T cells are depleted during priming, because activated CD4 T cells in the rat are MHC-II + (40). However, we observed a significant reduction of B cells upon Ab treatment, which raises the interesting question as to whether B cells play a role as APCs in PIA.…”

Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells

“…Similar to cell surface radioiodinated control SC (Fig. 4C) strong a and p signals were obtained while only small quantities of terminally sialylated invariant chains p35 and p45 were expressed at the cell surface still in association with the a / p two-chain complex [20]. When 3-day cultured LC-B were compared with fresh LC-B an up-regulation of class I1 complexes during short-term culture was again noticed.…”

Immune regulation in self tolerance: functional elimination of a self‐reactive, counterregulatory CD8+ T lymphocyte circuit by neonatal transfer of encephalitogenic CD4+ T cells lines

“…The specificity of the neonatal transfer effect was corroborated in a third group of Lewis rats, which had been treated neonatally with activated BS83 line cells. This T cell line originates from a BS rat, recognizes the same MBP epitope in the same Ia context as Lewis T lines, and is able to transfer mild EAE to Lewis rats when given at high dosages [11]. Rats of this group were fully susceptible to EAE induction after the first Q4 injection at the age of 8 weeks.…”