title: Immunodominant minor histocompatibility antigen peptides recognized by cytolytic T lymphocytes primed by indirect presentation.
abstract: BACKGROUND
  Indirect presentation of minor histocompatibility antigens (HA) as revealed by cross-priming of H2 heterozygous recipients effectively primes minor HA-specific cytolytic T lymphocytes (CTLs). However, it is not known if indirect priming generates CTLs specific for the same set of immunodominant minor HA recognized by CTLs primed by direct spleen cell injections.
  
  
  METHODS
  In order to indirectly prime minor HA-specific CTLs, we implanted (C57BL/6 x B6.C-H2d)F1 recipients with BALB.B and BALB/c splenocytes loaded into immunoisolation devices that effectively preclude direct donor:host contact. Responder spleen cells from these recipients were stimulated in vitro to expand BALB.B- and BALB/c-specific CTLs to reveal classical cross-priming.
  
  
  RESULTS
  Tests of CTL specificity using (1) CXB recombinant inbred strain targets that express different arrays of BALB/c minor HA and (2) high-performance liquid chromatography fractions of peptides from BALB.B Kb and Db molecules revealed that anti-BALB.B CTLs were specific for two previously identified dominant peptides, CTT-2 and CTT-5, presented by Kb molecules. Variation of responders and priming cells resulted in CTL responses to additional dominant peptides that had been identified previously with CTLs generated by direct priming with spleen cell injections. Indirect priming was not limited to this set of peptides recognized by CTLs in vitro because devices loaded with cells devoid of the CTL-detected peptides primed for accelerated skin allograft rejection.
  
  
  CONCLUSIONS
  Indirect presentation of minor HA in vivo stimulates the generation of CTLs specific for a subset of dominant minor HA peptides recognized by CTLs primed by direct presentation.
authors.affiliation: Department of Surgery, The Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Nevala
authors.forename: C
authors.initials: C
authors.lastname: Paul
authors.forename: P J
authors.initials: PJ
authors.lastname: Wettstein
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006579:Heterozygote; D007959:Lymphocyte Culture Test, Mixed; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000032:analysis / Q000276:immunology*; D011995:Recombination, Genetic; D016038:Skin Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D015778:Minor Histocompatibility Antigens