Review Article

Is There a Role for HTLV-1-Specific CTL in Adult T-Cell Leukemia/Lymphoma?

Table 1

HBZ and Tax as CTL target antigens: genetics, expression, and antigenicity in ATLL.

TaxHBZ

Naturally occurring genetic and epigenetic changes in ATLL

Point mutationsDetected in Tax 11–19 A*0201 epitope [25]None described

DeletionsPremature stop codons [26]None described
Deletions of 5′end of genome [25, 27, 28]

Epigenetic silencingHypermethylation of 5′LTR [46, 59, 60] and pX region [59]None described

Expression in ATLL

In vivomRNA and protein low/undetectable [45, 46]Multiply spliced isoforms of mRNA detected [51, 52]

Ex vivo culturesIncreased mRNA transcription in vitro culture [54]Increased mRNA transcription after culture in vitro [54]
Protein detected in 50% of ATL cases [44]Protein at threshold for detection using currently available antibodies [53]

CTL response in AC and HAM/TSP

CTL response in vivoHigh frequencies Tax-specific CTL detected in 66–94% infected individuals [12, 15, 43]Low frequencies of HBZ-specific CTL detectable in 25–40% of individuals [42, 43]

Immunogenicity for CTLImmunodominant, HTLV-1 protein most frequently recognized by CTL [1214]Peptides bind weakly to HLA class-1 in general [42]
Highly sensitive, cytotoxic CTL which recognise HBZ 26–34 in the context of A*0201 can be generated in vitro [53]

Potential for protection in ATLLEnhanced ability to present Tax peptides does not confer a significant protective effect [42] but can lyse ATL cells expressing Tax in vitro [23, 24]Efficient presentation of HBZ peptides significantly associated with low PVL and remaining asymptomatic [42]