Survival of the fittest or best adapted– H 1 , rgfe 2 Guido Forni 2 , , Sold Ferrone 3 , Choudhury Aniruddha 1 , Barbara Seliger 4 , Rolf Kiessling 1 1 Instit en za Instit gy Pathology, School of Medicine, Pittsburgh, USA Medical Immunology, Martin Lu rma (M itica opla easing evidence the MHC antigens not only regulate antitum immune responses in experimental animal mo but directly correlate with survival and prognosi with diverse types of cancers. M may in the future function as pote ection nition of antigenic peptides by CD8 + T s in the context of MHC class I and class II molecules on the surface of antigen- presenting cells is one of the initial steps that prime the adaptive immune system to respond to invading pathogens as well as potentially cancerous cells. MHC class I molecules are therefore essential components of the adaptive immune system (1) and critical to the immunological recognition of tumour expression and/or tumour cells with r cognition and destruction by the studies analysing associations between HLA frequency and cancer incidence as well as prognosis, are still limited. HC) mplex (MHC), antigens (HLA) short arm of one of the most l regions in ome has been characterized by m (LD) creating ons of correspond to This arrangement of genes that seases through ing’ single-nucleotides the number of g process (11) . ic definition of a characterized by strong LD, rather b (12) and extend s. The adjacent sequences within the superlocus contain several and demonstrate ut 28% of the genes within the d in the immune unexpected that large number of d diseases (14) . ocus is the high es and the high degree of polymorphism within the genes encoding peptide-presenting molecules (HLADPB1, -DQB1, - DQA1, -DRB1, -C, -B and -A). "Ancestral haplotype" (AH) is a term used to describe conserved haplotypes that appear to be identical among individuals not known to be directly related. These AHs have a specific content of alleles at all MHC loci and have a particular genomic length. In the Caucasoid population, some 30 AHs, and LA- biomarkers for prognosis and allow sel cancer patients for intensive therapy. Introduction cells. As a result defects in the function of MHC antigens provide an escape f om re dependent tumour development Giuseppe V. Masucci 1 , Emilia Andersson Villabona 1 , Hildur Helgadottir 1 , Kjell Be Federica Cavallo Lisa ldt 1 , ano host’s immune system (2) , (3, 4) . (5) (6) The number of Dept Oncology-Pathology, Karolinska Karolinska University Hospital, SE-171 Stockholm, Swed ute, 76 52, ute, and PA, ther ny The major histocompatibility complex (M The major histocompatibility co referred to as the human leukocyte in humans, is located on the chromosome 6 (6p21.3). It is intensively studied chromosoma humans. Recently, the human gen depicted in block-like structures areas of high linkage disequilibriu so-called haplotype blocks, separated by regi low LD hypothesized to recombination hot spots (7, 8) (9, 10) . greatly facilitates the discovery predispose individuals to di ‘haplotype-tagg 2 Molecular Biotechnology Center, Via Niz 10126 Torino, Italy 3 University of Pittsburgh Cancer Departments of Surgery, Immunolo 4 Institute of University Halle-Wittenberg, Halle/Saale, Ge Abstract The Major Histocompatibility complex comprises a set of genes that are cr immunity and surveillance against ne transformation. There is incr HC) l to stic that our dels s of polymorphism (SNPs), reducing markers needed in the mappin Haplotype blocks are an algorithm region in the human genome reduced haplotype diversity or than a biological phenomenon. The HLA loci typically span 3.6 M to 7.6 Mb with the telomeric repeat patients antigens HC ntial of genes regulating immune function synteny to the mouse MHC (12, 13) . Abo expressed transcripts from the superlocus are potentially implicate response. For this reason, it is not this genetic region is linked to a autoimmune and immune-mediate One characteristic of the MHC l degree of LD found between allel The recog lymphocyte HLA_A2rev_1_22.doc 1