Yersinia-hsp60-reactive T cells are efficiently stimulated by peptides of 12 and 13 amino acid residues in a MHC class II (I-Ab)-restricted manner

Abstract

SUMMARYHeat shock proteins (hsp) are immunodominant antigens in microbial infections. Previous work from this laboratory demonstrated that Yersinia-hsp60 (Y-hsp60)-reactive CD4 + ® ¯T cells play an important role for resolution of Y. enterocolitica infections in mice. In the present study we identified two epitopes of Y-hsp60 recognized by CD4 Th1 cell clones. The epitopes comprise 12 (214-225) and 13 (74-86) amino acid (aa) residues of Y-hsp60, and are the first described for MHC class II (I-A b ) molecules. Both epitopes are also recognized by T cells isolated from mesenteric lymph nodes from mice orogastrically infected with yersiniae. Stimulation of T cells with peptides of 12 and 13 aa residues of Y-hsp60 caused highly efficient proliferation compared with longer peptides, full-length recombinant Y-hsp60, or heatkilled Yersinia (HKY). Incubation of antigen-presenting cells with chloroquine blocked both peptide and HKY-triggered T cell proliferation, whereas cytochalasin B only blocked HKY-induced proliferation and to a lesser extent peptide-induced proliferation. The identified epitopes reside in a region of Yhsp60 that is conserved between Enterobacteriaceae but highly variable when compared with murine or human hsp60. Although both epitopes are identical to the related sequence of hsp60 (GroEL) of Escherichia coli, only weak T cell responses were observed upon stimulation with GroEL of E. coli, suggesting that other factors, e.g. flanking amino acid residues, might be important for antigen processing and T cell stimulation in a class II-restricted manner. Furthermore, these observations might be of significance for the rational design of subunit vaccines.

groEL Encodes a Highly Antigenic Protein in Burkholderia pseudomallei

“…Chaperonins are immunodominant proteins in microbial infections, and GroEL has been investigated for use in vaccination against bacterial infections such as tuberculosis, brucellosis, and yersiniosis (2,16,19). From our results, the GroEL of B. pseudomallei was further shown to be closely associated with humoral immunity.…”

Y. enterocolitica and Y. pseudotuberculosis

“…was reported (Autenrieth et al, 1992b). Today it is well established that Yersinia infection leads to strong T cell responses including CD 4 and CD 8 T cells, and that the T cells are involved in control of Yersinia (Autenrieth et al, 1992b;Autenrieth et al, 1993;Bohn and Autenrieth, 1996;Noll and Autenrieth, 1996;Bohn et al, 1998a). In fact, mice deficient in T cells are unable to control the pathogen and therefore develop chronic progressive and fatal infection.…”

Autodisplay: Development of an Efficacious System for Surface Display of Antigenic Determinants inSalmonellaVaccine Strains

“…The mechanism of protection against a number of gastrointestinal pathogens has been shown to depend on the induction of protective CD4 ϩ T cells (9,16,29,32,36). For example, peptides that bind to major histocompatibility complex (MHC) class II molecules conferring at least partial protection have been defined for rotavirus (4) and Yersinia enterocolitica (36).…”

“…For example, peptides that bind to major histocompatibility complex (MHC) class II molecules conferring at least partial protection have been defined for rotavirus (4) and Yersinia enterocolitica (36). A CD4 ϩ -T-cell dependent immune response is primarily induced when exogenous antigens are taken up by antigen-presenting cells, degraded in the phagolysosome and the derived peptide fragments are subsequently presented by MHC class II molecules to naive T cells (reviewed in reference 13).…”

“…The natural passenger domains of several autotransporter proteins have recently been replaced by heterologous proteins or protein domains, resulting in display of these determinants on the cell surface of gram-negative bacteria (23-25, 30, 42). In the present study we generated a translational fusion of an MHC class II-restricted epitope of the Y. enterocolitica heat shock protein Hsp60 consisting of amino acids 74 to 86 (Hsp60 [74][75][76][77][78][79][80][81][82][83][84][85][86] ) (36) to the autotransporter domain of the E. coli adhesin involved in diffuse adherence AIDA-I (1). Surface localization of the Hsp60 74-86 epitope in a Salmonella enterica serovar Typhimurium vaccine strain and the in vivo stability of the generated constructs were analyzed.…”