Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain

Table 1 Jchain-derived peptides identified by peptide elution and mass spectrometry from MM cell lines UM9 or U266 presented in HLA-A1, -A2, -A3, -A11 or -A24

	Sequence	Jchain aa	Eluted from	HLA-I^c	%Rank_EL^d	WB/SB^e	HLA binding
	Sequence	Position^a	MM cell line^b	HLA-I^c	%Rank_EL^d	WB/SB^e	Confirmed^f
YTA-A1	YTAVVPLVY	132–140	UM9	A1	0.02	SB	Yes
TAV-A1	TAVVPLVY	133–140	UM9	A1	1.30	WB	Yes
VLA-A2¹	VLAVFIKAVHV	10–20	U266	A2	3.22	< WB	Yes
VLA-A2²	VLAVFIKAV	10–18	UM9 and U266	A2	0.23	SB	Yes
YTA-A2	YTAVVPLV	132–139	UM9	A2	4.17	< WB	Yes
ISD-A3	ISDPTSPLRTR	72–82	U266	A3	3.16	< WB	Yes
RII-A11	RIIVPLNNR	61–69	UM9	A11	0.24	SB	Yes
ISD-A11	ISDPTSPLRTR	72–82	UM9	A11	1.90	WB	Yes
CYT-A24	CYTAVVPLV	131–139	U266^g	A24	0.96	WB	Yes

^aAmino acid (aa) position of identified peptides within the Jchain protein according to UniProt
^bUM9 cells (HLA-A1, -A11, -B7, -B35, -C3 and -C7 positive) were HLA-A2-transduced and U266 cells (HLA-A2, -A3, -B7, -B40, -C3, and -C7 positive) were HLA-A24-transduced
^cMost likely HLA-I origin of peptides based on HLA typing of MM cells from which peptides were eluted and peptide-binding motifs of these HLA alleles according to NetMHC4.0
^dRank of the predicted binding score for the eluted peptide to the respective HLA molecule compared to a set of random natural peptides
^ePeptides were annotated as weak or strong binders using the netMHC4.1 default setting of 0.5% rank for strong binders (SB) and 2% rank for weak binders (WB). Peptides with %Rank > 2.0 were annotated as < WB
^fPeptide binding to the respective HLA allele was investigated by peptide-HLA monomer refolding. Yes: peptide-HLA monomers were successfully refolded and remained stable. No: peptide-HLA monomers could not stably be refolded
^gEpitope identified in HLA-peptide elution experiment using anti-HLA-A1/A24 antibody but not in elution using pan HLA-I antibody W6-32

ISSN: 1756-8722