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ERAP2 (Endoplasmic Reticulum-Associated Aminopeptidase 2)

ERAP2 (Endoplasmic Reticulum-Associated Aminopeptidase 2). plays a role in resistance to HIV-1 infection. PhD student: Irma Saulle irma.saulle@unimi.it Poster: MOPDA0102. University of Milan.

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ERAP2 (Endoplasmic Reticulum-Associated Aminopeptidase 2)

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  1. ERAP2(Endoplasmic Reticulum-Associated Aminopeptidase 2) plays a role in resistance to HIV-1 infection PhD student: Irma Saulle irma.saulle@unimi.it Poster: MOPDA0102 University of Milan ERAP2 trims peptides to optimal size for loading onto MHC I molecules and shapes the antigenic repertoire presented to CD8+ T lymphocytes N 8-9 aa residues C ERAP2 ERAP2 Basic groove

  2. Introduction ERAP2 gene organization gtAagga Haplotype A Haplotype B gtGagga ERAP2 960 aa 120KDa ERAP2-FL AIMS To confirm the correlation between ERAP2 haplotypes and susceptibility to HIV-1 infection To understand the mechanism of action of the two haplotypes ERAP2-AS ERAP2 534 aa 60KDa Stop codons

  3. Results Association study for rs2549782 in HESN homoA subjects are protected from HIV-1 infection Co-segregation analysis of HLA-B*57 with rs2549782 genotypes in HESN and HIV+ HESN phenotype is associated with the co-presence of the HLA-B*57 allele and the homoA status at ERAP2

  4. BB BB BB BB BB BB 35 Homo-A (27%) 64 Hetero-AB (43%) 40 Homo-B (30%) AA AA AA AA AA AB AB AB AB AB Results mRNA basal expression for ERAP2-FL, ERAP2-AS and ERAP2-TOT ERAP2-FL P < 0.005 P < 0.005 140 120 P < 0.005 100 ERAP2-AS 80 NFOLD P < 0.005 60 40 20 ERAP2-TOT 0 HomoA HeteroAB HomoB NFOLD P < 0.05 P < 0.005 HomoA HeteroAB HomoB NFOLD Subjects with different ERAP2 genotype express different amounts of ERAP2 HomoA HeteroAB HomoB

  5. Results P < 0.005 P < 0.005 P < 0.005 PBMC CD4+ P < 0.005 P < 0.005 P < 0.005 Subjects with different ERAP2 genotype show a different susceptibility to HIV-1 infection HLA- ABC Mean fluorescence intensity p24 (pg/ml) log 10 HIV-infected PBMC Uninfected PBMC The expression of genes involved in antigen processing and presentation, and MHC class I molecules are increased in homoA subjects

  6. Conclusion ERAP2 mRNA levels MHC class I molecules Subjects with different ERAP2 genotypes show different expression of : Antigen processing & presentation pathway Different alleles of ERAP2 are able to generate a diverse antigen repertoire capable of activating different and likely more protective lymphocyte clones. 6

  7. Infectious Disease Unit S.M. Annunziata Hospital, Firenze Dr. Sergio Lo Caputo Dr. Francesco Mazzotta Chair of Immunology University of Milan Prof. Mario Clerici Prof. Daria Trabattoni Dr. Mara Biasin Dr. Mariacristina De Luca Dr. Francesca La Rosa Dr. Federica Gnudi Dr. Veronica Rainone Dr. Micaela Garziano Dr. Salomè Ibba Dr. Sara Yahyaei Dr. Angela Berzi Scientific Institute for Recovery and Care E. Medea Dr. Manuela Sironi Dr. Rachele Cagliani Infectious Disease and Microbiology Clinical Unit Valme Hospital, Spain Dr. Juan Macìas Dr. Juan A. Pineda Dr. Antonio Caruz PhD student: Irma Saulle University of Milan Email: irma.saulle@unimi.it

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