The immunoinformatics of cancer immunotherapy.

We review here the developments in the field of immunoinformatics and their present and potential applications to the immunotherapeutic treatment of cancer. Antigen presentation plays a central role in the immune response, and as a result in immunotherapeutic methods such as adoptive T-cell transfer and antitumor vaccination. We therefore extensively review the current technologies of antigen presentation prediction, including the next generation predictors, which combine proteasomal processing, transporter associated with antigen processing and major histocompatibility complex (MHC)-binding prediction. Minor histocompatibility antigens are also relevant targets for immunotherapy, and we review the current systems available, SNEP and SiPep. Here, antigen presentation plays a key role, but additional types of data are also incorporated, such as single nucleotide polymorphism data and tissue/cell-type expression data. Current systems are not capable of handling the concept of immunodominance, which is critical to immunotherapy, but efforts have been made to model general aspects of the immune system. Although tough challenges lie ahead, when measuring the field of immunoinformatics on its contributions thus far, one can expect fruitful developments in the future.

The nature of recombination in HLA-B*4207.

The identification of the novel human leukocyte antigen (HLA)-B*4207 allele, which was found in a blood donor of Caucasian origin, is described. The sequence of the new allele differs from HLA-B*4201 in three nucleotide substitutions in exon 2, resulting in three consecutive amino acid (AA) exchanges at position 69, 70, and 71. AA positions 69 and 70 affect the peptide-binding site of the HLA molecule in the formation of pockets A, B, and C. Therefore, it is likely that the peptide-binding motif of HLA-B*4207 differs from the HLA-B*4201 motif. HLA-B*4207 exhibits a high level of structural homology to HLA-B*08 alleles as well as to HLA-B*4201. Rating of the AA variations of these alleles according to the AA distance matrix score gives the lowest overall matching score between the HLA-B*4207 and the HLA-B*0801 alleles, indicating a high functional similarity. To further address this, homology modeling was performed using B8 as the closest structural template. The portion of the molecule that is accessible to the T-cell receptor and antibodies is identical between B*4207 and B*0801. Under consideration of allele frequencies, close inspection of these sequences shows that the new allele is most likely a result of a recombination involving B*0702 and B*0801. Unfortunately, patient consent could not be obtained for retrospective serological typing to definitively determine whether B*4207 reacts in the B8 serological group.

Peptide-binding characteristics of the novel allele DRB1*0112 are probably identical to DRB1*0101.

So far 11 different amino acid variants of the HLA-DRB1*01 family have been reported. We here describe the identification of a new HLA-DRB1*01 allele in a healthy female Caucasian. The allele was detected by sequencing-based typing during high-resolution typing of a potential unrelated donor from the North German Bone Marrow Registry (NKR). Compared with DRB1*010101, to which it is closest, the new variant is characterized by a new replacement mutation (G-->T) at nucleotide position 202 of exon 2, resulting in the amino acid substitution Arg-->Leu at position 72. Because this amino acid position is not involved in peptide binding or T-cell interaction, it is likely to represent a permissive mismatch to the more common HLA-DRB1*0101 allele.