Down-regulation of class I1 major histocompatibility complex molecules on antigen presenting cells after interaction with helper T cells
The recognition of antigenic peptides by CD4+ helper Tcells is demonstrated here to result in a dramatic (up to 90%) decrease in expression of major histocompatibility complex (MHC) class I1 molecules on the surface of antigenpresenting cells (APC). The reduction is selective to the class I1 isotype presenting the antigen, but if affects both allelic forms of the same isotype in heterozygous APC. The observed MHC down-regulation requires a specificT cell receptor-peptide-class I1 interaction, a direct contact between T cell and APC, and the involvement of CD2 molecules. These findings have important implications for the regulation of immune response, self tolerance, and autoimmunity.
Materials and methods
2.1 Antigens
Tetanus toxoid peptide 830-844 (TT, COOH-Gln-Tyr-Ile-Lys-Ala-Asn-Ser-Lys-Phe-Ile-Gly-Ile-Thr-Glu-Leu-NH~), flu virus hemagglutinin peptide 307-319 (HA, COOH-Pro-Lys-Tyr-Val-Lys-Gln-Asn-Thr-Leu-Lys-Leu-Ala-Thr-NH2), and its substitution analogs (HA-Q, COOH-Pro-Lys-Tyr-Val-Lys-Gln-Gln-Thr-Leu-Lys-Leu-Ala-Thr-NH2; HA-LLL, COOH-Pro-Lys-Tyr-Val-Leu-Leu-Leu-Thr-Leu-Lys-Leu-Ala-Thr-NH2) were synthetized by the solid-phase method, and purified by reverse-phase HPLC. The DRbinding affinity of HA and its analogs was determined by measuring (concentration of peptide required for 50% inhibition of binding of 30 pmol radiolabeled HA to