CHT HLA Genetics & Molecular Biology 2 — Questions and Answers
Question 1: What is the primary function of beta-2 microglobulin (β2m) in HLA class I molecules?
- Stabilizes the alpha chain and is required for surface expression (Correct answer)
- Directly binds the peptide antigen
- Anchors the molecule to the cell membrane
- Signals intracellularly after antigen recognition
Correct answer: Stabilizes the alpha chain and is required for surface expression
β2m is a non-covalently associated light chain that stabilizes the HLA class I alpha chain and is essential for proper folding and surface expression.
Question 2: Which type of HLA typing method directly determines the nucleotide sequence of HLA alleles?
- Sequence-Based Typing (SBT/SBT-NGS) (Correct answer)
- Serological microlymphocytotoxicity
- Low-resolution SSP
- Complement-dependent cytotoxicity
Correct answer: Sequence-Based Typing (SBT/SBT-NGS)
SBT (Sanger sequencing) and NGS-based methods directly read the nucleotide sequence to assign high-resolution HLA alleles.
Question 3: An HLA allele designated HLA-A*02:01 indicates what level of resolution?
- Second-field (allele-level) resolution (Correct answer)
- First-field (antigen-group) resolution only
- Protein-level expression status
- Serological split antigen
Correct answer: Second-field (allele-level) resolution
The two-field nomenclature (e.g., 02:01) specifies the allele group (02) and the specific allele within that group (01), representing allele-level resolution.
Question 4: Which HLA gene is encoded outside the classical MHC class I region yet is important in NK cell regulation?
- HLA-E (Correct answer)
- HLA-A
- HLA-B
- HLA-C
Correct answer: HLA-E
HLA-E is a non-classical class I molecule encoded within the MHC that presents leader-sequence peptides and serves as a primary ligand for NK cell NKG2 receptors.
Question 5: What does 'cis' configuration refer to in the context of HLA DQ heterodimers?
- Alpha and beta chains encoded on the same chromosome (Correct answer)
- Alpha and beta chains from opposite parental chromosomes
- Homozygous DQ alleles at both loci
- Trans-species allele sharing
Correct answer: Alpha and beta chains encoded on the same chromosome
A cis DQ heterodimer is formed by DQA1 and DQB1 chains encoded on the same parental haplotype/chromosome.
Question 6: Which molecular typing technique uses allele-specific primers to amplify target HLA sequences?
- SSP (Sequence-Specific Primers) (Correct answer)
- SSOP (Sequence-Specific Oligonucleotide Probes)
- SBT (Sequence-Based Typing)
- Flow cytometry crossmatch
Correct answer: SSP (Sequence-Specific Primers)
SSP uses primers designed to amplify only specific alleles or allele groups under defined PCR conditions, providing rapid low-to-intermediate resolution typing.
CHT HLA Genetics & Molecular Biology 2
What is the primary function of beta-2 microglobulin (β2m) in HLA class I molecules?