Characterisation of the novel HLA-B*58:02:04 allele by next-generation sequencing.

HLA-B*58:02:04 differs from HLA-B*58:02:01 by one synonymous nucleotide in codon 215 in exon 4.

Characterization of the novel HLA-B*40:538 allele by next-generation sequencing.

The HLA-B*40:538 allele differs from HLA-B*40:01:02:01 at position 905 C→T in exon 5.

Detection of the HLA-C*07:04:29 allele in a Chinese individual.

HLA-C*07:04:29 differs from HLA-C*07:04:01:01 by a single substitution in exon 4.

Identification of the novel HLA-C allele, HLA-C*07:02:150.

A novel HLA-C*07 allele, now officially designated HLA-C*07:02:150, was identified by next-generation sequencing.

The novel HLA-C*07:02:147 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-C*07:02:147 differs from HLA-C*07:02:01:01 by one synonymous nucleotide substitution in exon 2.

The novel HLA-C*03:94:02 allele identified by next-generation sequencing in a Chinese individual.

HLA-C*03:94:02 differs from HLA-C*03:94:01 by a single nucleotide substitution in exon 2 (codon 17 GGA->GGG).

Detection of the novel HLA-B*55:01:31, HLA-C*07:1113 alleles and confirmation of HLA-C*12:392.

Novel HLA-B*55:01:31, HLA-C*07:1113 alleles and confirmatory HLA-C*12:392 allele were detected during the HLA typing process.

Untranslated regions (UTRs) are a potential novel source of neoantigens for personalised immunotherapy.

Background: Neoantigens, mutated tumour-specific antigens, are key targets of anti-tumour immunity during checkpoint inhibitor (CPI) treatment. Their identification is fundamental to designing neoantigen-directed therapy. Non-canonical neoantigens arising from the untranslated regions (UTR) of the genome are an overlooked source of immunogenic neoantigens. Here, we describe the landscape of UTR-derived neoantigens and release a computational tool, PrimeCUTR, to predict UTR neoantigens generated by start-gain and stop-loss mutations. Methods: We applied PrimeCUTR to a whole genome sequencing dataset of pre-treatment tumour samples from CPI-treated patients (n = 341). Cancer immunopeptidomic datasets were interrogated to identify MHC class I presentation of UTR neoantigens. Results: Start-gain neoantigens were predicted in 72.7% of patients, while stop-loss mutations were found in 19.3% of patients. While UTR neoantigens only accounted 2.6% of total predicted neoantigen burden, they contributed 12.4% of neoantigens with high dissimilarity to self-proteome. More start-gain neoantigens were found in CPI responders, but this relationship was not significant when correcting for tumour mutational burden. While most UTR neoantigens are private, we identified two recurrent start-gain mutations in melanoma. Using immunopeptidomic datasets, we identify two distinct MHC class I-presented UTR neoantigens: one from a recurrent start-gain mutation in melanoma, and one private to Jurkat cells. Conclusion: PrimeCUTR is a novel tool which complements existing neoantigen discovery approaches and has potential to increase the detection yield of neoantigens in personalised therapeutics, particularly for neoantigens with high dissimilarity to self. Further studies are warranted to confirm the expression and immunogenicity of UTR neoantigens.

Identification of the novel HLA-B*13:191 allele by next-generation sequencing.

The novel HLA-B*13:191 allele was detected during the HLA typing for kidney transplantation.

Characterization of the novel HLA-C*06:376N allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.

Detection of two HLA-B*35 variants: HLA-B*35:01:01:39 and -B*35:03:01:32.

Two nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-B*35:01:01:39 and -B*35:03:01:32.

The novel HLA-B*46:01:42 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*46:01:42 differs from HLA-B*46:01:01:01 by one nucleotide in exon 5.

The novel HLA-C*06:372 allele, identified in a stem cell donor of an old order mennonite ethnicity.

HLA-C*06:372 differs from HLA-C*06:02:01:01 by a single substitution in exon 4.

Identification of the novel HLA-B*40:06:01:18 allele in a North Indian individual.

HLA-B*40:06:01:18 differs from HLA-B*40:06:01:02 by one nucleotide change in the 5'UTR (T > C).

The novel HLA-C*08:273 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2.

NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2.

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID-19.

Identification of the novel HLA-C*14:159 allele by next-generation sequencing.

The novel HLA-C*14:159 allele was detected during the routine HLA typing for kidney transplantation.

A novel HLA-C*17 variant, HLA-C*17:01:01:29, identified in a healthy individual from Greece.

HLA-C*17:01:01:29 differs from the HLA-C*17:01:01:05 allele by one nucleotide substitution in the 3'UTR.

A novel HLA-C*04 variant, HLA-C*04:01:01:174, identified in a healthy individual from Greece.

HLA-C*04:01:01:174 differs from the HLA-C*04:01:01:06 allele by one nucleotide substitution in the intron 5.

A novel HLA-C*01 variant, HLA-C*01:02:01:70, identified in a healthy individual from Greece.

HLA-C*01:02:01:70 differs from the HLA-C*01:02:01:01 allele by one nucleotide substitution in the intron 4.