Two adjacent nucleotide substitutions in exon 2 characterize the novel class II HLA‐DPB1*687:01 allele.

A novel HLA-DPB1 allele, named HLA-DPB1*647:01, identified in a leukemia patient.

A novel HLA-DPB1 allele, named HLA-DPB1*647:01, identified in a leukemia patient.

A novel HLA‐DPB1 allele, named HLA‐DPB1*647:01, identified in a leukemia patient.

A novel HLA‐DPB1 allele, named HLA‐DPB1*647:01, identified in a leukemia patient.

The novel HLA‐C*04:288 differs from HLA‐C*04:01:01:06 by a single nucleotide substitution in exon 2.

Two novel alleles, HLA-A*31:125 and HLA-B*44:269, are described in Italian bone marrow donors.

Two novel alleles, HLA‐A*31:125 and HLA‐B*44:269, are described in Italian bone marrow donors.

Two novel alleles, HLA-A*31:125 and HLA-B*44:269, are described in Italian bone marrow donors.

One nucleotide substitution at residue 142 of the HLA-DRB1*13:01:01 results in a new allele, HLA-DRB1*13:215.

One nucleotide substitution at residue 142 of the HLA‐DRB1*13:01:01 results in a new allele, HLA‐DRB1*13:215.

One nucleotide substitution at residue 142 of the HLA-DRB1*13:01:01 results in a new allele, HLA-DRB1*13:215.

The killer cell immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA) interaction represents an example of genetic epistasis, where the concomitant presence of specific genes or alleles encoding receptor-ligand units is necessary for the activity of natural killer (NK) cells. Although KIR and HLA genes segregate independently, they co-evolved under environmental pressures to maintain particular KIR-HLA functional blocks for species survival. We investigated, in 270 Italian healthy individuals, the distribution of KIR and HLA polymorphisms in three climatic areas (from cold north to warm south), to verify their possible geographical stratification. We analyzed the presence of 13 KIR genes and genotyped KIR ligands belonging to HLA class I: HLA-C, HLA-B and HLA-A. We did not observe any genetic stratification for KIR genes and HLA-C ligands in Italy. By contrast, in a north-to-south direction, we found a decreasing trend for the HLA-A3 and HLA-A11 ligands (P = 0.012) and an increasing trend for the HLA-B ligands carrying the Bw4 epitope (P = 0.0003) and the Bw4 Ile80 epitope (P = 0.0005). The HLA-A and HLA-B KIR ligands were in negative linkage disequilibrium (correlation coefficient -0.1211), possibly as a consequence of their similar function in inhibiting NK cells. The distribution of the KIR-HLA functional blocks was different along Italy, as we observed a north-to-south ascending trend for KIR3DL1, when coupled with HLA-B Bw4 ligands (P = 0.0067) and with HLA-B Bw4 Ile80 (P = 0.0027), and a descending trend for KIR3DL2 when coupled with HLA-A3 and HLA-A11 ligands (P = 0.0044). Overall, people from South Italy preferentially use the KIR3DL1-HLA-B Bw4 functional unit, while those from the North Italy equally use both the KIR3DL2-HLA-A3/A11 and the KIR3DL1-HLA-B Bw4 functional units to fight infections. Thus, only KIR3DL receptors, which exert the unique role of microbial sensors through the specific D0 domain, and their cognate HLA-A and HLA-B ligands are selectively pressured in Italy according to geographical north-to-south distribution.

A novel HLA-DPB1 allele, named DPB1*296:01, was identified in the Thai mother of a hematologic patient.

A novel HLA-DPB1 allele, named DPB1*296:01, was identified in the Thai mother of a hematologic patient.

A newly identified allele, named HLA B*15:276 , differs from B*15:01:01:01 by the single nucleotide substitution 511T‐C at codon 147 (Trp → Arg) in exon 3.

A novel HLA‐DPB1 allele, named DPB1*296:01, was identified in the Thai mother of a hematologic patient.

A novel HLA-A allele, HLA-A*68:105, was detected by sequence-based typing (SBT) in an Italian bone marrow donor. It differs from HLA-A*68:01:02 at five nucleotides, three intronic, nt 699 T->G (intron 2), nt 705 T->C (intron 2) and nt 2770 G->A (intron 7), and two located in exon 3, at positions 726 A-G (codon 94 Ile->Val) and 733 T-G (codon 97 Arg->Met), respectively.

The new HLA DRB1*01:54 differs from DRB1*01:02:01 by one nucleotide at exon 2.

A novel HLA‐B*51:01:29 allele differs from B*51:01:01 at one nucleotidic position in the exon 3.