Administration of PLP139–151 Primes T Cells Distinct from Those Spontaneously Responsive In Vitro to This Antigen

Abstract

We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139–151 by Vβ-Jβ spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement Vβ10-Jβ1.1, but naive mice do not; in contrast, TCR CDR3-β rearrangements of Vβ18-Jβ1.2 and Vβ19-Jβ1.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLP139–151 presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, Vβ10-Jβ1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced Vβ10-Jβ1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect Vβ18-Jβ1.2 and Vβ19-Jβ1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP139–151 primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This “immunized” repertoire substitutes for the naive one and becomes dominant at the time of disease onset.

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

“…3A, right column). This frequency is comparable to that seen in SJL mice after immunization with p139 in adjuvant as previously reported (6) and confirmed in this study by the data reported in the same Fig. 3A (one positive of four mice injected with p139 in adjuvant; Fig.…”

“…The spontaneous repertoire was depleted at the same time also from the spleens (data not shown). These data are consistent with the hypothesis that the p139-specific spontaneous repertoire was recruited and in part already depleted by rMS p139 to a similar extent as that seen following immunization with p139 in adjuvant (6).…”

“…As a source of DCs that had processed MPT64-p139 in vivo, female SJL mice were infected with rMS p139 , and 4 days later, DCs from the draining LNs were enriched as described in Materials and Methods. This method results in a population enriched in DCs and able to stimulate p139-specific BV10 (and BV4) T cells without the need for addition of Ag in vitro (6,29). As a source of BV10 and BV4 cells, three SJL mice were immunized with p139 emulsified in CFA.…”

“…First, an appropriate T cell repertoire has to be activated. In fact, activated self-reactive T cells of healthy and sick individuals belong to distinct repertoires in both experimental and human autoimmune diseases (6,7). Second, polarization of T cells toward a pathogenic phenotype needs to be induced.…”

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

“…Similarly, we have shown that T cell repertoires are different in pathogenic and nonpathogenic autoimmune responses in human disease and experimental models (40,46). We therefore asked if cell localization ( H PE-⌬MPT64-BCG versus H ⌬MPT64-BCG) and amount of antigen produced ( H PE-⌬MPT64-BCG versus 33 PE-⌬MPT64-BCG) impact T cell repertoire selection and if differences in the composition of the MPT64-specific repertoire were correlated with protection.…”