Suppression of blastogenesis and proliferation of activated CD4+ T cells: intravenous immunoglobulin (IVIg) versus novel anti-human leucocyte antigen (HLA)-E monoclonal antibodies mimicking HLA-I reactivity of IVIg

(a) Based on the differences in their HLA class Ia and Ib reactivity, the anti-HLA-E mAbs are categorized into eight types. Type 1 [Terasaki Foundation Laboratory (TFL)-033] reacted only with HLA-E and not with any other HLA class I alleles; type 5 (TFL-037) did not recognize HLA-F and HLA-G; and type 8 (TFL-006 and TFL-007) reacted with all HLA class Ia and Ib alleles. The common shared peptide sequences are exposed in the open conformer in the absence of β2-microglobulin 15
Types of anti-HLA-E mAbs	Non-classical HLA-Ib			Classical HLA-Ia			Names of mAbs
Types of anti-HLA-E mAbs	HLA-E	HLA-F	HLA-G	HLA-A	HLA-B	HLA-Cw	Names of mAbs
Type 1	+	−	−	−	−	−	TFL-033
Type 2	+	+	−	−	−	−
Type 3	+	−	+	−	−	−
Type 4	+	+	+	−	−	−
Type 5	+	−	−	+	+	+	TFL-037
Type 6	+	+	−	+	+	+
Type 7	+	−	+	+	+	+
Type 8	+	+	+	+	+	+	TFL-006 & TFL-007

(b) Reactivity (determined by mean fluorescent intensity, MFI) of the undiluted culture supernatants of the mAbs on different human leucocyte antigen (HLA) class I alleles. Note that TFL-033 and TFL-037 did not recognize the heavy chains of HLA-F and HLA-G. The differences in MFI among the mAbs are critical to an understanding of the possible binding site of the mAbs on the cell surface of activated T lymphocytes
Isotype	TFL-033	TFL-037	TFL-006	TFL–007		TFL-033	TFL-037	TFL-006	TFL–007		TFL-033	TFL-037	TFL-006	TFL-007
Isotype	IgG1	IgG2b	IgG2a	IgG2a		IgG1	IgG2b	IgG2a	IgG2a		IgG1	IgG2b	IgG2a	IgG2a
Neg	3	8	15	7	B^*0702(B7)			1 331	841	CW^*0102(Cw1)		674	7 242	3 268
Pos	71	103	88	85	B^*0801(B8)			2 092	1 033	CW^*0202(Cw2) [J]		2 662	10 690	6 084
HLA-E	24 411	13 025	22 522	21 618	B^*1301(B13)		3 684	5 654	3 979	CW^*0302(Cw10)		1 321	5 917	3 062
HLA-F			12 650	11 035	B^*1302(B13)		1 568	2 237	1 426	CW^*0303(Cw9)		2 212	7 114	4 250
HLA-G			7 193	2 670	B^*1401(B64)		9 268	11 319	8 767	CW^*0304(Cw10)		1 846	6 584	3 891
A^*0101(A1)			2 395	1 037	B^*1402(B65)		1 492	4 414	2 558	CW^*0401(Cw4)			2 843	1 272
A^*0201(A2)			856		B^*1501(B62) [R]			1 097		CW^*0501(Cw5)		10 015	16 131	13 096
A^*0203(A2)			1 095		B^*1502(B75)		5 150	6 256	4 497	CW^*0602(Cw6)		1 060	9 396	4 274
A^*0206(A2)			1 494	843	B^*1503(B72)		1 016	2 831	1 926	CW^*0702(Cw7)		753	12 251	6 919
A^*0301(A3)			818		B^*1510(B71)			2 616	1 470	CW^*0801(Cw8)		7 709	13 456	10 733
A^*1101(A11) [J,R]		7 062	10 190	8 476	B^*1511 (B75)		5 715	9 041	5 902	CW^*1203(Cw12)			5 055	2 102
A^*1102(A11)			860		B^*1512(B76)		956	1 624	996	CW^*1402(Cw14)		2 129	8 727	4 936
A^*2301(A23)			614		B^*1513(B77)		4 650	5 326	3 365	CW^*1502(Cw15) [R]		1 574	6 030	3 225
A^*2402(A24) [J]		1 287	3 133	2 011	B^*1516(B63)		3 591	5 614	3 443	CW^*1601(Cw16)		1 109	8 462	4 364
A^*2403(A24)		1 005	3 151	1 967	B^*1801(B18)		4 185	6 990	4 890	CW^*1701(Cw17)		1 433	13 521	9 069
A^*2501(A25)			1 230	692	B^*2705(B27)		702	2 591	1 576	CW^*1802(Cw18)		15 389	17 918	15 207
A^*2601(A26)			3 368	1 638	B^*2708(B27)		1 438	4 437	2 671	Cw^* alleles	0	14	16	16
A^*2901(A29)		1 465	3 194	2 256	B^*3501(B35)		8 235	10 205	8 594
A^*2902(A29)			2 235	1 136	B^*3701(B37)		3 039	6 472	4 338
A^*3001(A30)			2 229	1 237	B^*3801(B38)			3 844	1 820
A^*3002(A30)		994	3 353	2 211	B^*3901(B39)		4 068	7 093	5 304
A^*3101(A31)			858		B^*4001(B60)		2 518	5 743	3 758
A^*3201(A32)		1 053	2 237	1 508	B^*4002(B61)		4 032	6 118	4 675
A^*3301(A33) [R]		928	2 791	1 627	B^*4006(B61)		14 399	15 643	13 758
A^*3303(A33)		2 215	4 212	2 961	B^*4101(B41)		3 721	7 191	5 277
A^*3401(A34)		1 643	6 268	3 968	B^*4201(B42)			636
A^*3402(A34)			1 399	893	B^*4402(B44)		1 342	7 062	4 059
A^*3601(A36)		1 694	5 806	3 826	B^*4403(B44)		4 459	7 256	5 638
A^*4301(A43)		789	4 420	2 364	B^*4501(B45)		5 725	9 535	7 646
A^*6601(A66)			3 644	1 526	B^*4601(B46)		3 924	6 491	4 130
A^*6602(A66)			1 395	789	B^*4701(B47)		2 152	6 528	3 895
A^*6801(A68)			1 314	859	B^*4801(B48)		1 254	4 365	2 716
A^*6802(A68)			2 078	1 276	B^*4901(B49)
A^*6901(A69)			1 964	917	B^*5001(B50)			741
A^*7401(A74)			723		B^*5101(B51)		1 634	6 205	3 724
A^*8001(A80)			2 841	1 430	B^*5102(B51)		2 082	5 251	3 579
A^* alleles	0	11	32	24	B^*5201(B52)		1 538	4 524	2 728
					B^*5301(B53)		6 270	8 807	7 323
					B^*5401(B54)		3 122	5 556	4 153
					B^*5501(B55)		1 326	2 829	1 887
					B^*5601(B56)			1 386	777
					B^*5701(B57)
					B^*5703(B57)			1 229	600
					B^*5801(B58) [R]		7 525	10 160	8 047
					B^*5901(B59)		1 211	5 646	3 001
					B^*6701(B67)			675
					B^*7301(B73)		1 271	3 347	2 171
					B^*7801(B78)		3 373	6 089	4 597
					B^*8101(B81)			1 352	729
					B^*8201(B82)		2 195	4 367	3 069
					B^* alleles	0	37	48	44
Letters J and R after HLA class I alleles refers to the typing of the donors who have provided T cells for this study.

(c) The number of HLA-A, HLA-B, HLA-Cw alleles recognized by type 8 mAbs TFL-006 and TFL-007 compared with the number of HLA alleles recognized by different therapeutic preparations of intravenous immunoglobulin (IVIg)
IVIgs versus TFL mAbs	Reactivity of different HLA class I antigens
	Classical HLA-Ia alleles			Non-classical HLA-Ib
	HLA-A	HLA-B	HLA-Cw	HLA-E	HLA-F	HLA-G
IVIg (GamaStan, USA)	31	49	16	+	+	+
IVIg (Octagam, Mexico)	30	47	16	+	+	+
IVIg (GlobEx, India)	20	39	16	+	+	+
TFL-006 (formerly PTER006)	31	48	16	+	+	+
TFL-007 (formerly PTER007)	26	44	16	+	+	+
TFL-037 (formerly PTER037)	11	37	14	+	0	0
TFL-033 (formerly PTER033)	0	0	0	+	0	0

Table 1.