CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes.
CD91, the endocytic receptor for alpha2-macroglobulin (alpha2M), mediates the internalization of certain heat shock proteins (hsps) and the cross-presentation of peptides they chaperone by antigen-presenting cells. The phylogenetic conservation of the immunologically active CD91 ligands, alpha2M and hsps, is consistent with the idea of an ancestral system of immune surveillance. We have further explored this hypothesis by taking advantage of the frog Xenopus, and asked how conserved is CD91 and whether the expression of CD91 is differentially modulated during immune responses of class I-positive adult and naturally class I-negative larvae. We have identified a Xenopus CD91 gene homologue that displays high sequence identity (>65%) with other CD91 homologues and contains an additional distinctive cytoplasmic NPXY motif. Phylogenetic analysis indicates that CD91 homologues branch as a monophyletic group distinct from other LDLRs; this suggests an origin of CD91 contemporary with that of metazoans. A 14-kb transcript is detected by Northern blotting in most adult and larval tissues, including lymphoid tissues. RT-PCR study reveals that CD91 is expressed in most cell types, including adult macrophages, B and T cells as well as in splenocytes and thymocytes from naturally MHC class I negative larvae. CD91 is markedly up-regulated in vivo by adult peritoneal leukocytes following bacterial and viral stimulation; it is constitutively expressed on class I-negative larval peritoneal leukocytes at high levels and cannot be further upregulated by such stimulation. These data are in agreement with a conserved role of CD91 in immunity.
Marr
Shauna
S
Department of Microbiology and Immunology,, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Goyos
Ana
A
Gantress
Jennifer
J
Maniero
Gregory D
GD
Robert
Jacques
J
D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007814:Larva / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits; D015854:Up-Regulation; D014981:Xenopus / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D021122:Protein Subunits